THE EFFECTS OF SOME NATURAL PROSTAGLANDINS ON ISOLATED HUMAN CIRCULAR BRONCHIAL MUSCLE
P.J. Gardiner Research Department, Miles Laboratories Limited, Stoke Court, Stoke Poges, Buckinghamshire. (England)
ABSTRACT PGE 1 relaxed isolated human circular bronchial muscle over a wide concentration range as did isoprenaline° Surprisingly isoprenaline was more potent than PGE.. PGF9~ weakly contracted this muscle preparation whereas histamine was more potent. PGE2, however, produced paradoxical results, relaxing some tissues and contracting others, always in a concentration-related manner irrespective of tissue tone. In preparations that contracted to PGE2, tachyphylaxis induced to PGF 2 also applied to PGE^, but did not affect PGElerelaxations or histamine contractions. These findings suggest that PGE 2 can stimulate either PGF9~ or PGE 1 receptors of isolated human bronchial ~ s c l e . ACKNOWLEDGEMENTS The technical assistance of Miss A.A. Butt, Miss J. Copas and Mr. R.D. Elliott is greatly appreciated. The assistance of Mr. J.W. Jackson and Sister De Mulder, of Harefield Hospital and the staff at the Brompton Hospital in obtaining specimens of human lung is greatly appreciated. i0 -7 -75
PROSTAGLANDINS OCTOBER 1975
VOL. 10 NO. 4
607
PROSTAGLANDINS
INTRODUCTION
Previous work showed that PGE~ relaxed and PGF~ contracted isolated human bronchial muscle; z~ PGEg, however, usually relaxed it but was less potent that PGEI(1). These in vitro results were confirmed in vivo when PGE., E^ and F2~ were a d m i n i s t e r e - d ~ aerosols t6 asthmatics (2, 3, 4 and 5). On various occasions, however, PGE^ produced paradoxical responses both in vitr~ and in vivo (6, 7, 8 and 9). The present w o r k was intended to clarify the activity of these E and F prostaglandins, using a wide range of concentrations and numerous preparations of isolated human bronchial muscle. MATERIALS
AND METHODS
Spirals of bronchial muscle were cut from apparently normal lung tissue obtained from surgery for carcinoma of the lung, and stored overnight at 0 C in Krebs-Henseleit solution. On the following day each spiral was suspended , o in Krebs-Henseleit solution at 37 C in a i0 ml bath aerated w i t h 5 per cent carbon dioxide in oxygen. The muscle was allowed to equilibrate for 90 min before the experiment began. Test substances in 0.9 per cent w / v sodium chloride in wate~ were added to the batch for 2-5 min. Responses were measured isotonically using a Harvard isotonic transducer with a load of 250 mg. Prostaglandins used were from Ono Pharmaceuticals Ltd., isoprenaline sulphate B.P. was from the Wellcome Foundation and histamine acid phosphate was a BDH Chemical.
608
O C T O B E R 1975
VOL. 10 NO. 4
0% %O
©
©
©
©
1
-95+-11 (35) -116+-15 (28)
-76+_27 (i0)
i. 0 i0.0
i00.0
-162+-22.7 (6) -172.5+-28.3 (6)
+26+-5 (13) +68+_8 (13)
+14+_5 (12)
+17.4+10(3)
PGF2a
*, response is mm movement of recording pen
+, mean concentration
-, mean relaxation
+51.5+8 (6)
+7+_15 ( 2 3 ) +36+_8.5 (18)
-113.5+--20(6)
-34.3+--11.8(6)
-32+--7(2)
-9.5+--5.5(20)
-25.6_+6.7(14)
0.01
Isoprenaline
0.1
-7.5+--7(5)
PGE 2 -5.3+2.4 (3)
PGE 1
ram. Mean response* + standard error (ni~ber tissues tested)
0.001
Concentration ~g/ml
The effects of 3 natural prostaglandins, isoprenaline and histamine on isolated h~nan bronchial muscle.
TART~
+107.6+26 (5)
+60.4+_12.3 (5)
+36+--8.9(5)
+6.4+--1.1(5)
Histamine
©
©
< ©
©
©
0%
71.8+40 (6)
1.0
I00.0
0
of recording pen
51.5+8.1 (6)
44.2+7.5 (16)
34.7+_7 (17)
9+--1.5(I0)
13 (I)
mean concentration
*, response is ran m o v ~ t
+, mean ooncentration
-, mean relaxation
26+11 (2)
27.7+--7(i0)
0.1
i0.0
12.7+--5.5 (4)
mean relaxation
+51.5+8.1 (6)
+36+--8.6 (18)
+7+_14.8 (23)
-9.4+--5.5 (20)
-7.6+--7(5)
overall mean
Human bronchial muscle n~n response* for PGE 2 ~ standard error (number tissuesused)
0.01
Concentration ~g/ml
The variable activity of PGE 2 on isolated h~nanbronchial muscle.
Table II
>
©
PROSTAGLANDINS
FIG. 1 PGE
2
ACTIVITY
ON
HUMAN B R O N C H I A L MUSCLE IN VITRO
100 Z 0 80 I(.J
P.J. Gardiner Research Department, Miles Laboratories Limited, Stoke Court, Stoke Poges, Buckinghamshire. (England)
ABSTRACT PGE 1 relaxed isolated human circular bronchial muscle over a wide concentration range as did isoprenaline° Surprisingly isoprenaline was more potent than PGE.. PGF9~ weakly contracted this muscle preparation whereas histamine was more potent. PGE2, however, produced paradoxical results, relaxing some tissues and contracting others, always in a concentration-related manner irrespective of tissue tone. In preparations that contracted to PGE2, tachyphylaxis induced to PGF 2 also applied to PGE^, but did not affect PGElerelaxations or histamine contractions. These findings suggest that PGE 2 can stimulate either PGF9~ or PGE 1 receptors of isolated human bronchial ~ s c l e . ACKNOWLEDGEMENTS The technical assistance of Miss A.A. Butt, Miss J. Copas and Mr. R.D. Elliott is greatly appreciated. The assistance of Mr. J.W. Jackson and Sister De Mulder, of Harefield Hospital and the staff at the Brompton Hospital in obtaining specimens of human lung is greatly appreciated. i0 -7 -75
PROSTAGLANDINS OCTOBER 1975
VOL. 10 NO. 4
607
PROSTAGLANDINS
INTRODUCTION
Previous work showed that PGE~ relaxed and PGF~ contracted isolated human bronchial muscle; z~ PGEg, however, usually relaxed it but was less potent that PGEI(1). These in vitro results were confirmed in vivo when PGE., E^ and F2~ were a d m i n i s t e r e - d ~ aerosols t6 asthmatics (2, 3, 4 and 5). On various occasions, however, PGE^ produced paradoxical responses both in vitr~ and in vivo (6, 7, 8 and 9). The present w o r k was intended to clarify the activity of these E and F prostaglandins, using a wide range of concentrations and numerous preparations of isolated human bronchial muscle. MATERIALS
AND METHODS
Spirals of bronchial muscle were cut from apparently normal lung tissue obtained from surgery for carcinoma of the lung, and stored overnight at 0 C in Krebs-Henseleit solution. On the following day each spiral was suspended , o in Krebs-Henseleit solution at 37 C in a i0 ml bath aerated w i t h 5 per cent carbon dioxide in oxygen. The muscle was allowed to equilibrate for 90 min before the experiment began. Test substances in 0.9 per cent w / v sodium chloride in wate~ were added to the batch for 2-5 min. Responses were measured isotonically using a Harvard isotonic transducer with a load of 250 mg. Prostaglandins used were from Ono Pharmaceuticals Ltd., isoprenaline sulphate B.P. was from the Wellcome Foundation and histamine acid phosphate was a BDH Chemical.
608
O C T O B E R 1975
VOL. 10 NO. 4
0% %O
©
©
©
©
1
-95+-11 (35) -116+-15 (28)
-76+_27 (i0)
i. 0 i0.0
i00.0
-162+-22.7 (6) -172.5+-28.3 (6)
+26+-5 (13) +68+_8 (13)
+14+_5 (12)
+17.4+10(3)
PGF2a
*, response is mm movement of recording pen
+, mean concentration
-, mean relaxation
+51.5+8 (6)
+7+_15 ( 2 3 ) +36+_8.5 (18)
-113.5+--20(6)
-34.3+--11.8(6)
-32+--7(2)
-9.5+--5.5(20)
-25.6_+6.7(14)
0.01
Isoprenaline
0.1
-7.5+--7(5)
PGE 2 -5.3+2.4 (3)
PGE 1
ram. Mean response* + standard error (ni~ber tissues tested)
0.001
Concentration ~g/ml
The effects of 3 natural prostaglandins, isoprenaline and histamine on isolated h~nan bronchial muscle.
TART~
+107.6+26 (5)
+60.4+_12.3 (5)
+36+--8.9(5)
+6.4+--1.1(5)
Histamine
©
©
< ©
©
©
0%
71.8+40 (6)
1.0
I00.0
0
of recording pen
51.5+8.1 (6)
44.2+7.5 (16)
34.7+_7 (17)
9+--1.5(I0)
13 (I)
mean concentration
*, response is ran m o v ~ t
+, mean ooncentration
-, mean relaxation
26+11 (2)
27.7+--7(i0)
0.1
i0.0
12.7+--5.5 (4)
mean relaxation
+51.5+8.1 (6)
+36+--8.6 (18)
+7+_14.8 (23)
-9.4+--5.5 (20)
-7.6+--7(5)
overall mean
Human bronchial muscle n~n response* for PGE 2 ~ standard error (number tissuesused)
0.01
Concentration ~g/ml
The variable activity of PGE 2 on isolated h~nanbronchial muscle.
Table II
>
©
PROSTAGLANDINS
FIG. 1 PGE
2
ACTIVITY
ON
HUMAN B R O N C H I A L MUSCLE IN VITRO
100 Z 0 80 I(.J
