Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Waterloo on 01/04/15 For personal use only.
COMMUNICATIONS
spontaneous activity appeared to be equally sensitive to the action of the purine. Also, adenosine and its nucleotide were less effective depressants of the superficial, glutamate-excited cerebral cortical neuroiles than of spontaneously active neurones of the deeper layers (Kostopoulos and Phillis 1977). The action of AMP on Renshaw cells is in keeping with the observation that adenosine decreases the quanta1 content of the endplate potentials in the rat diaphragm (Ginsborg and Hirst 1972). Moreover, adenine nucleotides reduce the release of ACh in the guinea pig ileum preparation, and in slices of the rat cerebral cortex (Vizi and Knoll 1976). ATP (but not GTP and CTP) strongly inhibits transmitter release in Torpedo electroplaques (Israel et al. 1977), indicating that the specific presynaptic depressant action is due to the adenine component of the molecule. Adenine nucleotides thus appear to have a very general depressant effect on transmitter release from cholinergic terminals. If they are indeed released from purinergic terminals (Burnstock 1975) or from postsynaptic cells (1sr;el ef al. 1977), they could exert a significant modulating action on central synaptic activity. BURNSTOCK,G. 1975. Purinergic transmission. In Handbook of psychopharmacology. Vol. 5. Edited by L. L. Iversen, S. D. Iversen, and S. N . Snyder. Raven Press, New York. pp. 131-194.
1393
ECCLES,J. C., FATT,P., and KOKETSU,K. 1954. Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones. J. Physiol. (London), 126,524-562. GINSBORG, B. L., and HIRST,S . D. 1972. The effect of adenosine on the release of the transmitter from the phrenic nerve of the rat. J. Physiol. (I,ondon), 224, 629-645. HOLTON,P. 1959. The liberation of adenosine triphssphate on antidromic stimulation of sensory nerves. J. Physiol. (London), 145,494-504. ISRAEL, M., LESBATS, R., MANARANCHE, J., MARSAL, J., PI~ASTOUR-FRACHON, P., and MEUNIER,F. M. 1977. Related changes in amounts of ACh and ATP in resting and active Torpedo nerve electroplaque synapses. J. Neurochem. 28, 1259-1267. K o s ~ o ~ o u ~6. o sK.. , and PHILLIS,J. W. 1977. Purinergic depression of neurones in different areas of the rat brain. Exp. Neurol. 55, 719-724. PHILLIS,J. W., and K o s ~ o ~ o u r oG. s , K. 1975. Adenosine as a putative transmitter in the cerebral cortex. Studies with potentiators and antagonists. Life Sci. 17, 1085-1094. PHILLIS,J. W., KOSTOPOULOS, G. K., and LIMACHER, J. J. 1974. Depression of corticospinal cells by various purines and pyrimidines. Can. J. PhysioI. Pharmacol. 52, 1226-1229. Pun., I., and MGILWAIN, H. 1972. Adenine derivatives as neurohumoral agents in the brain. The quantities libcrated on excitation of superfused cerebral tissues. Riochem. J. 130,975-98 1. D. A. 1977. MicroiontoSTONE,T. W., and TAYLOR, phoretic studies of the effects of cyclic nucleotides on excitability of neurones in the rat cerebral cortex. J. Physiol. (London), 266, 523-543. VEI, E. S., and KNOLL,J. 1976. The inhibitory effect of adenosine and related nucleotides on the release of acetylcholine. Neuroscience, 1, 391-398.
The effects of cholecystokinin and cholecystokinin-octapeptide on intestinal lymph flow in the rat S. e.TURNER AND J. A. BARROWMAN Faculty of Medicine. Memorinl University of Newfound/and, St. Jolzn's, Nfid., Canada A I B 3V6 Received August 15, 1977 J. A. 1977. The effects of cholecystokinin and TURNER,S. G., and BARROWMAN, cholecystokinin-octapeptide on intestinal lymph flow in the rat. Can. J. Physiol. Pharmacol. 55, 1393-1396. Intravenous cholecystokinin and its synthetic C-terminal oetapeptide were found to cause a transient augmentation of intestinal lymph flow in the rat. Concomitant increase in lymph protein transport suggests that this reflects the increase in intestinal blood flow which is known to occur in response to these agents.
ABBREVIATIONS: CCK, cholecystokinin; CCK-OP, cholecystokinin-octapeptide.
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Waterloo on 01/04/15 For personal use only.
1394
CAN. J. PHYSIBL. PWARMACOL.
Intasduction The selective action of CCK in augmenting blood flow in the splanchnic bed has been groposed as a mechanism for the postprandial increase in blood flow to the intestine (Fara et al. 1969 ) . Long-chain and medium-chain triglyceride feeding increases intestinal lymph flow and protein transport in that lymph (Simrnonds 1955; Turner and Barrowman 1977). The excess protein carried in intestinal lymph following feeding is thought to be derived by filtration from the plasma (Wollin and Jaques 1973). Thus, postprandial lymph flow changes may be partly brought about by enhanced splanchnic blood flow and intestinal capillary filtration due to CCK release. The present study was designed to investigate the influence of CCK and the synthetic C-terminal octapeptide (CCK-OP) on intestinal lymph flow.
Materials and Methods Experimental Animals Male Wistar rats 4200-400 g) were operated on under anaesthesia (Nernbutal, 30 rng/kg). Through a right subcostal incision the main lymphatic trunk draining the small intestine was cannulated (Intramedic PE 50 tubing) and a soft feeding tube tied into the ducxienum (Blue Line Infant Feeding Tube, Portex, U.K.). Isotonic saline was continuously given through the latter at 2.5 ml/h; intestinal lymph was collected from the former into citrated tubes. The duodenal infusion served to offset the Boss of fluid from the lymphatic fistula. An intravenous Iine was established by introducing fine tubing (Intramedic PE 10, Clay Adams, U.S.A.) into one of the three large veins in the tail with the aid of a 20-@ needle. This was kept open, without the use of an anticoagulant, by pumping isotonic saline very slowly through (just under 0.5 ml/ h ) . After operation, animals were kept in restraining cages and left in a warm room overnight. iMarerinls All sodium chloride solutions (saline) were isotonic (0.15 M ) . In the saline-alone experiments, 0.8 ml was given intravenously. CCK (-20% purity) was obtained from the GIM Research Unit of the Karolinska Institutet, Stockholm. A fresh vial containing 75 Ivy dog units was opened just before each experiment and reconstituted with 7.5 ml of isotonic salines Of this, 0.1 ml ( 1 lJ) was given intraveno~msIv.washed in with 0.7 ml saline. CCK-OP - ( ~ i n c a l i d e - ~ i n e v a cwas ) a gift of E. R. ~ q u i b b& sons, Inc., Montreal, P.Q. A new vial was opened for each experiment and the 5 pg reconstructed with 14.2 ml sterile water (USP, pyrogen-free). Of this, 0.1 ml (35 ng) was given intravenously, followed by 0.7 nml saline. The same solution was used 4 h later
VOL. 55.
1977
for the repeat dose. Potency of CCK-OP in aqueous solution is reported not to decline within 24 h at room temperature (E. R. Squibb & Sons, Inc.). Experin~entalDesign Experiments were performed the day after surgery on conscious, restrained animals. Intestinal lymph was collected in 20-min intervals. ( a ) After a control period to establish basal levels, three animals were given saline intravenously followed after 2 h by CCK. In one animal the experiment was extended to allow a second dose of CCK to be given. ( b ) Following a 2-h control period, CCK-OP was given intravenously to five animals. After 2 h this was followed by saline, and after a further 2 h by a second dose of CCK-OP. Lymph Analysis Lymph was colIected continuously and the weight secreted measured at 28-min intervals. Protein was assayed using the biuret reaction (Weichselbaum 1946), first clearing the lymph of its opacity by ultracentrifugation at 120 000 g for 1 h and removing the supernatant layer of chylomicra.
Results Of the eight animals given intravenous saline none showed any changes in intestinal lymph flow or protein transport. Following CCK, three out of three animals showed an increase (about 100% of control) in lymph flow (Fig. 1 ). The increase was both immediate and short lasting, the response being over within 20 min. Simultaneously, total protein carried in the lymph increased. The one animal given a repeat dose of CCK showed very similar increases in flow and protein transport to the first dose (broken line, Fig. 1) . Of the five animals given CCK-OP, four showed an increase in lynnph flow and protein transport (increase of about 50% of control with the first dose, slightly less with the second) (Fig. 2). Again the-response was rapid and over. The fifth animal had a similar increase in flow after the first dose of CCK-OP to the other four, but the flow failed to return to control levels for the remaining 6 h of the its high flow rate this lymph was the lymph flowing lo" in protein 'Ontent at an increased rate following CCK or CCK-OP. It is unlikely that CCK-OP was responsible for such a long-lasting effect and this result has not been included in the .graph. ~h~ explanation for protein lransport preceding the the increase second dose of CCK-OP is not clear.
COMMUNICATIONS
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Waterloo on 01/04/15 For personal use only.
INTESTINAL LYMPH
--.*--*.**
lMEST lNAL LYMPH
ml 1 20 min
FLOW
1.5
0.5
120
1
2%)
t
360
440
T
CCK CCK FIG.1. Intestinal lymph flow and protein transport in response to intravenous isotonic sodium chloride solution and 1 Ivy dog unit of CCK. Solid lines represent the mean of three anim~alls; broken lines represent one animal given a second injection of CCK. Vertical lines represent the range. NaCl
Discussion One Ivy dog unit of the preparation of CCK used produced a definite and reproducible increase in intestinal lymph flow and protein transport in the rat. The brief duration of the response is in accord with reported values for the disappearance half-time of exogenous CCK of approximately 3 min in dogs and man (Rayford et al. 1975). The hormone preparation used was not highly purified and the possibility that impurities with vasoactive properties were present and responsible for the increase in lymph flow cannot be ignored. CCK is known to stimulate intestinal smooth muscle. However, this effect is unlikely to be the cause of the increase in flow of lymph as intestinal lymph flow is apparently to a large extent independent of gut motility( Simmonds 1957). In the cat and dog, CCK has been shown to increase superior mesenteric blood flow (Fara 1969; Biber et al. 1973; Fasth et a!. 1973; Thulin and Olsson 1973; Fara and Madden 1975), and it is suggested that this is the mechanism by which
lymph flow increased in the present experiments. The concomitant increase in protein carried by the lymph, presumably derived from the plasma, supports this idea. The C-terminal octapeptide of CCK has been shown to have all the biological properties of CCK, including augmentation of intestinal blood flow (Thulin 1973). Increase in lymph flow following CCK-OB occurred but was less clear-cut than after CCK, and of small magnitude, particularly after a second dose. The explanation of this observation is not clear. Enhanced lymph flow after CCK-OP administration supports the idea that the effects observed with the CCK preparation represent the action of that hormone rather than the effect of contaminating material with vasodilator properties. The estimate by Yau et al. (1974) of the relative potencies of CCK and CCK-OP on ileal rnuscle was taken in an attempt to approximate the doses of the hormone and the peptide fragment. However, potency in contracting intestinal smooth muscle may not necessarily reflect
CAN. J. PHYSIOL. PHARMACOL. VOL. 5 5 , 1977
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Waterloo on 01/04/15 For personal use only.
INTESTINAL LYMPH
0.5
40
440 CCK-OP
NaCl
CCK-OP
FIG.2. Intestinal lymph flow and protein transport in response to intravenous isotonic sodium chloride solution and 35 ng CCK-OP. Circles represent the means of four animals and the range is given by the vertical lines.
vasoactive potency, and it is necessary to explore this phenomenon over a range of doses of CCK-OP.
-1957. The relationship between intestinal motility and the flow and rate of fat output in thoracic duct lymph in unanaesthetized rats. Q.J. Exp. Physiol. 42, 205-221. THULIN,L. 1973. Effects of the C-terminal octapeptide RIBER, B., FARA,J. W., and LUNDGREN, 0. 1973. Vasof cholecystokinin on splanchnic circulation in the cular reactions in the small intestine during vasodog. Acta Chir. Scand. 139, 687-690. dilation. Acta Physiol. Scand. 89,449-456. FARA.J. W., and MADDEN, K. S. 1975. Effect of secre- THULIN,L., and OLSSON,P. 1973. Effects of pure natural cholecystokinin on splanchnic circulation in tin and cholecystokinin on small intestinal blood the dog. Acta Chir. Scand. 139, 681-686. flow distribution. Am. J. Physiol. 229, 1365-1 370. S. C., and BARROWMAN. 3. A. 1977. Intestinal E. H., and SONNENSCHLIN,TURNER, FARA,3. W., KUBINSTEIN, lymph flow and lymphatic transport of protein during K. R. 1969. Visceral and behavioural responses to fat absorption. Q.J. Exp. Physiol. 62, 175-180. intraduodenal fat. Science, 166, 1 10-1 11. T. E. 1946. An accurate and rapid FASTH,S., FILIPSSON, S., H U L T ~ N L.,, and MARTINSON. WEICHSELBAUM, method for the determination of proteins in small 3. 1973. The effect of the gastrointestinal hormones amounts in blood scrum and plasma. Am. J. Clin. on small intestine motility and blood flow. ExPathol. (Tech. Sect.), 10. 40-49. perientia, 29,982-984. L. B. 1973. Plasma protein RAYFORD, P. L., FENDER, H . R., RAMUS, N. I., REEDER, WOLLIN.A.. and JAQUES, escape from the intestinal circulation to the lymD. D., and THOMPSON, J. C . 1975. Release and halfphatics during fat absorption. Proc. Soc. Exp. Biol. life of CCK in man. I n Gastrointestinal hormones. bled. 142, 1114-1 117. Edited by 3. C. Thompson. University of Texas C . M., EDWARDS, L. E., and YAU.W. M., MAKIII~OUF, Press, Austin and London. FARRAR, J. T. 1974. The action of cholecystokinin SIMMONDS.W. J. 1955. Some observations on the and related peptides on guinea pig small intestine. increase in thoracic duct lymph flow during intestinal Can. J. Physiol. Pharmacol. 52, 298-303. absorption of fat in unanesthetized rats. Aust. J. Exp. Biol. Med. Sci. 33, 305-3 14.
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spontaneous activity appeared to be equally sensitive to the action of the purine. Also, adenosine and its nucleotide were less effective depressants of the superficial, glutamate-excited cerebral cortical neuroiles than of spontaneously active neurones of the deeper layers (Kostopoulos and Phillis 1977). The action of AMP on Renshaw cells is in keeping with the observation that adenosine decreases the quanta1 content of the endplate potentials in the rat diaphragm (Ginsborg and Hirst 1972). Moreover, adenine nucleotides reduce the release of ACh in the guinea pig ileum preparation, and in slices of the rat cerebral cortex (Vizi and Knoll 1976). ATP (but not GTP and CTP) strongly inhibits transmitter release in Torpedo electroplaques (Israel et al. 1977), indicating that the specific presynaptic depressant action is due to the adenine component of the molecule. Adenine nucleotides thus appear to have a very general depressant effect on transmitter release from cholinergic terminals. If they are indeed released from purinergic terminals (Burnstock 1975) or from postsynaptic cells (1sr;el ef al. 1977), they could exert a significant modulating action on central synaptic activity. BURNSTOCK,G. 1975. Purinergic transmission. In Handbook of psychopharmacology. Vol. 5. Edited by L. L. Iversen, S. D. Iversen, and S. N . Snyder. Raven Press, New York. pp. 131-194.
1393
ECCLES,J. C., FATT,P., and KOKETSU,K. 1954. Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones. J. Physiol. (London), 126,524-562. GINSBORG, B. L., and HIRST,S . D. 1972. The effect of adenosine on the release of the transmitter from the phrenic nerve of the rat. J. Physiol. (I,ondon), 224, 629-645. HOLTON,P. 1959. The liberation of adenosine triphssphate on antidromic stimulation of sensory nerves. J. Physiol. (London), 145,494-504. ISRAEL, M., LESBATS, R., MANARANCHE, J., MARSAL, J., PI~ASTOUR-FRACHON, P., and MEUNIER,F. M. 1977. Related changes in amounts of ACh and ATP in resting and active Torpedo nerve electroplaque synapses. J. Neurochem. 28, 1259-1267. K o s ~ o ~ o u ~6. o sK.. , and PHILLIS,J. W. 1977. Purinergic depression of neurones in different areas of the rat brain. Exp. Neurol. 55, 719-724. PHILLIS,J. W., and K o s ~ o ~ o u r oG. s , K. 1975. Adenosine as a putative transmitter in the cerebral cortex. Studies with potentiators and antagonists. Life Sci. 17, 1085-1094. PHILLIS,J. W., KOSTOPOULOS, G. K., and LIMACHER, J. J. 1974. Depression of corticospinal cells by various purines and pyrimidines. Can. J. PhysioI. Pharmacol. 52, 1226-1229. Pun., I., and MGILWAIN, H. 1972. Adenine derivatives as neurohumoral agents in the brain. The quantities libcrated on excitation of superfused cerebral tissues. Riochem. J. 130,975-98 1. D. A. 1977. MicroiontoSTONE,T. W., and TAYLOR, phoretic studies of the effects of cyclic nucleotides on excitability of neurones in the rat cerebral cortex. J. Physiol. (London), 266, 523-543. VEI, E. S., and KNOLL,J. 1976. The inhibitory effect of adenosine and related nucleotides on the release of acetylcholine. Neuroscience, 1, 391-398.
The effects of cholecystokinin and cholecystokinin-octapeptide on intestinal lymph flow in the rat S. e.TURNER AND J. A. BARROWMAN Faculty of Medicine. Memorinl University of Newfound/and, St. Jolzn's, Nfid., Canada A I B 3V6 Received August 15, 1977 J. A. 1977. The effects of cholecystokinin and TURNER,S. G., and BARROWMAN, cholecystokinin-octapeptide on intestinal lymph flow in the rat. Can. J. Physiol. Pharmacol. 55, 1393-1396. Intravenous cholecystokinin and its synthetic C-terminal oetapeptide were found to cause a transient augmentation of intestinal lymph flow in the rat. Concomitant increase in lymph protein transport suggests that this reflects the increase in intestinal blood flow which is known to occur in response to these agents.
ABBREVIATIONS: CCK, cholecystokinin; CCK-OP, cholecystokinin-octapeptide.
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Waterloo on 01/04/15 For personal use only.
1394
CAN. J. PHYSIBL. PWARMACOL.
Intasduction The selective action of CCK in augmenting blood flow in the splanchnic bed has been groposed as a mechanism for the postprandial increase in blood flow to the intestine (Fara et al. 1969 ) . Long-chain and medium-chain triglyceride feeding increases intestinal lymph flow and protein transport in that lymph (Simrnonds 1955; Turner and Barrowman 1977). The excess protein carried in intestinal lymph following feeding is thought to be derived by filtration from the plasma (Wollin and Jaques 1973). Thus, postprandial lymph flow changes may be partly brought about by enhanced splanchnic blood flow and intestinal capillary filtration due to CCK release. The present study was designed to investigate the influence of CCK and the synthetic C-terminal octapeptide (CCK-OP) on intestinal lymph flow.
Materials and Methods Experimental Animals Male Wistar rats 4200-400 g) were operated on under anaesthesia (Nernbutal, 30 rng/kg). Through a right subcostal incision the main lymphatic trunk draining the small intestine was cannulated (Intramedic PE 50 tubing) and a soft feeding tube tied into the ducxienum (Blue Line Infant Feeding Tube, Portex, U.K.). Isotonic saline was continuously given through the latter at 2.5 ml/h; intestinal lymph was collected from the former into citrated tubes. The duodenal infusion served to offset the Boss of fluid from the lymphatic fistula. An intravenous Iine was established by introducing fine tubing (Intramedic PE 10, Clay Adams, U.S.A.) into one of the three large veins in the tail with the aid of a 20-@ needle. This was kept open, without the use of an anticoagulant, by pumping isotonic saline very slowly through (just under 0.5 ml/ h ) . After operation, animals were kept in restraining cages and left in a warm room overnight. iMarerinls All sodium chloride solutions (saline) were isotonic (0.15 M ) . In the saline-alone experiments, 0.8 ml was given intravenously. CCK (-20% purity) was obtained from the GIM Research Unit of the Karolinska Institutet, Stockholm. A fresh vial containing 75 Ivy dog units was opened just before each experiment and reconstituted with 7.5 ml of isotonic salines Of this, 0.1 ml ( 1 lJ) was given intraveno~msIv.washed in with 0.7 ml saline. CCK-OP - ( ~ i n c a l i d e - ~ i n e v a cwas ) a gift of E. R. ~ q u i b b& sons, Inc., Montreal, P.Q. A new vial was opened for each experiment and the 5 pg reconstructed with 14.2 ml sterile water (USP, pyrogen-free). Of this, 0.1 ml (35 ng) was given intravenously, followed by 0.7 nml saline. The same solution was used 4 h later
VOL. 55.
1977
for the repeat dose. Potency of CCK-OP in aqueous solution is reported not to decline within 24 h at room temperature (E. R. Squibb & Sons, Inc.). Experin~entalDesign Experiments were performed the day after surgery on conscious, restrained animals. Intestinal lymph was collected in 20-min intervals. ( a ) After a control period to establish basal levels, three animals were given saline intravenously followed after 2 h by CCK. In one animal the experiment was extended to allow a second dose of CCK to be given. ( b ) Following a 2-h control period, CCK-OP was given intravenously to five animals. After 2 h this was followed by saline, and after a further 2 h by a second dose of CCK-OP. Lymph Analysis Lymph was colIected continuously and the weight secreted measured at 28-min intervals. Protein was assayed using the biuret reaction (Weichselbaum 1946), first clearing the lymph of its opacity by ultracentrifugation at 120 000 g for 1 h and removing the supernatant layer of chylomicra.
Results Of the eight animals given intravenous saline none showed any changes in intestinal lymph flow or protein transport. Following CCK, three out of three animals showed an increase (about 100% of control) in lymph flow (Fig. 1 ). The increase was both immediate and short lasting, the response being over within 20 min. Simultaneously, total protein carried in the lymph increased. The one animal given a repeat dose of CCK showed very similar increases in flow and protein transport to the first dose (broken line, Fig. 1) . Of the five animals given CCK-OP, four showed an increase in lynnph flow and protein transport (increase of about 50% of control with the first dose, slightly less with the second) (Fig. 2). Again the-response was rapid and over. The fifth animal had a similar increase in flow after the first dose of CCK-OP to the other four, but the flow failed to return to control levels for the remaining 6 h of the its high flow rate this lymph was the lymph flowing lo" in protein 'Ontent at an increased rate following CCK or CCK-OP. It is unlikely that CCK-OP was responsible for such a long-lasting effect and this result has not been included in the .graph. ~h~ explanation for protein lransport preceding the the increase second dose of CCK-OP is not clear.
COMMUNICATIONS
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Waterloo on 01/04/15 For personal use only.
INTESTINAL LYMPH
--.*--*.**
lMEST lNAL LYMPH
ml 1 20 min
FLOW
1.5
0.5
120
1
2%)
t
360
440
T
CCK CCK FIG.1. Intestinal lymph flow and protein transport in response to intravenous isotonic sodium chloride solution and 1 Ivy dog unit of CCK. Solid lines represent the mean of three anim~alls; broken lines represent one animal given a second injection of CCK. Vertical lines represent the range. NaCl
Discussion One Ivy dog unit of the preparation of CCK used produced a definite and reproducible increase in intestinal lymph flow and protein transport in the rat. The brief duration of the response is in accord with reported values for the disappearance half-time of exogenous CCK of approximately 3 min in dogs and man (Rayford et al. 1975). The hormone preparation used was not highly purified and the possibility that impurities with vasoactive properties were present and responsible for the increase in lymph flow cannot be ignored. CCK is known to stimulate intestinal smooth muscle. However, this effect is unlikely to be the cause of the increase in flow of lymph as intestinal lymph flow is apparently to a large extent independent of gut motility( Simmonds 1957). In the cat and dog, CCK has been shown to increase superior mesenteric blood flow (Fara 1969; Biber et al. 1973; Fasth et a!. 1973; Thulin and Olsson 1973; Fara and Madden 1975), and it is suggested that this is the mechanism by which
lymph flow increased in the present experiments. The concomitant increase in protein carried by the lymph, presumably derived from the plasma, supports this idea. The C-terminal octapeptide of CCK has been shown to have all the biological properties of CCK, including augmentation of intestinal blood flow (Thulin 1973). Increase in lymph flow following CCK-OB occurred but was less clear-cut than after CCK, and of small magnitude, particularly after a second dose. The explanation of this observation is not clear. Enhanced lymph flow after CCK-OP administration supports the idea that the effects observed with the CCK preparation represent the action of that hormone rather than the effect of contaminating material with vasodilator properties. The estimate by Yau et al. (1974) of the relative potencies of CCK and CCK-OP on ileal rnuscle was taken in an attempt to approximate the doses of the hormone and the peptide fragment. However, potency in contracting intestinal smooth muscle may not necessarily reflect
CAN. J. PHYSIOL. PHARMACOL. VOL. 5 5 , 1977
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by University of Waterloo on 01/04/15 For personal use only.
INTESTINAL LYMPH
0.5
40
440 CCK-OP
NaCl
CCK-OP
FIG.2. Intestinal lymph flow and protein transport in response to intravenous isotonic sodium chloride solution and 35 ng CCK-OP. Circles represent the means of four animals and the range is given by the vertical lines.
vasoactive potency, and it is necessary to explore this phenomenon over a range of doses of CCK-OP.
-1957. The relationship between intestinal motility and the flow and rate of fat output in thoracic duct lymph in unanaesthetized rats. Q.J. Exp. Physiol. 42, 205-221. THULIN,L. 1973. Effects of the C-terminal octapeptide RIBER, B., FARA,J. W., and LUNDGREN, 0. 1973. Vasof cholecystokinin on splanchnic circulation in the cular reactions in the small intestine during vasodog. Acta Chir. Scand. 139, 687-690. dilation. Acta Physiol. Scand. 89,449-456. FARA.J. W., and MADDEN, K. S. 1975. Effect of secre- THULIN,L., and OLSSON,P. 1973. Effects of pure natural cholecystokinin on splanchnic circulation in tin and cholecystokinin on small intestinal blood the dog. Acta Chir. Scand. 139, 681-686. flow distribution. Am. J. Physiol. 229, 1365-1 370. S. C., and BARROWMAN. 3. A. 1977. Intestinal E. H., and SONNENSCHLIN,TURNER, FARA,3. W., KUBINSTEIN, lymph flow and lymphatic transport of protein during K. R. 1969. Visceral and behavioural responses to fat absorption. Q.J. Exp. Physiol. 62, 175-180. intraduodenal fat. Science, 166, 1 10-1 11. T. E. 1946. An accurate and rapid FASTH,S., FILIPSSON, S., H U L T ~ N L.,, and MARTINSON. WEICHSELBAUM, method for the determination of proteins in small 3. 1973. The effect of the gastrointestinal hormones amounts in blood scrum and plasma. Am. J. Clin. on small intestine motility and blood flow. ExPathol. (Tech. Sect.), 10. 40-49. perientia, 29,982-984. L. B. 1973. Plasma protein RAYFORD, P. L., FENDER, H . R., RAMUS, N. I., REEDER, WOLLIN.A.. and JAQUES, escape from the intestinal circulation to the lymD. D., and THOMPSON, J. C . 1975. Release and halfphatics during fat absorption. Proc. Soc. Exp. Biol. life of CCK in man. I n Gastrointestinal hormones. bled. 142, 1114-1 117. Edited by 3. C. Thompson. University of Texas C . M., EDWARDS, L. E., and YAU.W. M., MAKIII~OUF, Press, Austin and London. FARRAR, J. T. 1974. The action of cholecystokinin SIMMONDS.W. J. 1955. Some observations on the and related peptides on guinea pig small intestine. increase in thoracic duct lymph flow during intestinal Can. J. Physiol. Pharmacol. 52, 298-303. absorption of fat in unanesthetized rats. Aust. J. Exp. Biol. Med. Sci. 33, 305-3 14.
