The

influcncc

of the a,,%- adrcnoccptol

suhtypc-sclcclivc

cl’kc~ was osscsxd in the isolated rabbiI ventricular IO ;I mcmhronc

frnction

nmol/l)

( + )-Niguldipinc

affiniiy.

dcrivcd

from rabbit

ventricular

I + bniguldipinc on the a,-mcdiatcd positive inotrclpic ( +-)-Niguldipinc displaced IIIC spccil’ic binding of [‘H]praLosin

antagonist

myocardium.

muscle with high (K, = h4.h pmol/l; RI, = Xi)

displaced specific [‘H]CGP-121

177 hindinp only ;II very high conccnIrations

and low (K, = 7.OS (K, = I I8 nmol/l).

( t bNiguldipinc at 0.1 pmt)l/l and higher shiltcd the conccntr~ttion-rcsponsc CUIVC for IIIC rY,-mcdiatcdpositive inotropic cI‘t’crt downwards. hug ;It higher conccntr;lIions (up to II) and IO0 nmol/l) it did noI C;IUSC ;I further shili of the curve. ( + LNiguldipinc (I-I(10 nmcil/l) did not affect thr /I-mcriiatcd positive inotropic cfl’ccl nnd the IXKII lijrcc ol’conccntration. ( - )-Niguldipinc also showed ;I sclectivc inhibitory action on the rr,-atlrenoccptor-mcdialud positive inotropic cl’l’cck hut its affinity and pokncy were approximakly I-2 log uniIs lower than those of ( + 9-niguldipinc. The prcscnt results indicak Ihat the (Y,,-adrcnoccptor suhlype is involved in fhc rr,-nlcdiiltcd positive inotropic cffccl. ( t )-Niguldipinc (or ( - bniguldipinc with lower effinity) is ahlc IO hclcclivcly the cardiac IY,,,- adrcnoccptor-mcdialcd positive inotropic cffcct. The magnitutlc ol’ the a,,,-mcdialcd inotropic clTwl. howcvcr, may hc much less than Ihilt IllCdiiltcd by llic (Y,,,-subtype in llic r;ihhit ventricular myocardium.

;mIaponizc

( + )-Niguldipinc;

tr,,,-AtlrL’noccpIt,rs;

Positive inolp.jpic cfl’cc~: (3H]Pr;lzosin

Sympathomimctic through

amincs moduiatc: ~yocardial

activation

con-

of cardiac crl- as well as

Ij-ild~CllllCCplllrS in most tlliHlllllilli;~il spccics (Sclliim;lilil, IWW; SCIIOIZ. I WI; Endoh. IWI. 10~~19. The SUhiXllUlilr mcdiatcd

:.lccllilnisnl

of lhc positive inotropic

11): cu,-adrcnoccptors

is still

cffcct

LIII~CC dchatc.

Aclivation of c;lrdiilc cu,-adrcnoccptors ClcvittCs tl~ inlraccllular C‘il” transient (Endoh and Blinks. lOXX9. An increase in C.i12+ influx through silrc(~lcmmill L-typo n

of action

myocardium

ocardial CCIIS. n,-ildrcnoccptl~r-~~cdiatcd

1. Introduction

tractility

binding: VcnIricular

pcl!cntinl

(Apkon

honnc. IO,YX; Fcdida et ill.. 10X0. 1991; Ertl

and NsrCI ill.. IWI 9

and/or filcilitiltion of the Nil ‘-H ’ CxchilnyC: SYSIC~ (IwiIkur;l ct al.. IWO) may IW rcsponsihlc for 111~ CY,-

(rahhit)

CiL’

Signal-

ing involves the ;Wivi\tion of phoSpholip:lSc C. resulting in the stimuli~ti~ln of phosphoinosilidc hydrolysis (Brown Ct ill., I’1X.S: SClll~lZ Ct ill., I‘W Otani Ct ill., IOXX; Endoh ct ill., 1991 ). The SU~WX~UCII~ production of inositol 1, 4, S-triSphr)Sphiltc and dii~cylglyccrtll is p~~Stuli~t~dto play 311important role in signal trunsduction in scvcriil nc~ncilrdiuc tissues (Bcrridgc and Irvine. 10X4: Ahd~l-Liltif. IWO; Nishizuka. 1084. 108X9: the role of this process in the regulation of myocilrdial contractility has not ycl IWCn CStiil~liSllCd. N,-Adrcnoccptors hnvc hccn further sul~~l~~ssifi~d into e,,\- rcccptors (sclcctivcly hlockcd by WB 4101 OI 5-mcthylulapidil and coupled lcl L-IY~C Vi)‘+ cII;I~IIwI~). illld (Y1is-rcccptors (sclcctivcly hlockcd hy rhc irrcvcrsibll:

illkylilting

i\gcnt chlor~thylclor~idinc

pled to iIn ilccclcriltion

(Endoh

lulvc shown that prctrcatmcnt with chll~rcrhylclonidinc markedly inhihts the positive inotropic cffcct ilnd

and Blinks,

IWX;

Tcrzic

CI al.. 1002). In my-

hydrolysis9

in smooth IIILISC~CCCIIS (HiIn CI ill.. 1’187: Minncmun. 108X; Minncman et al.. I%%). In iI previous study. WC

phosplaoinositidc