Fe1-adrenoceptor subtypes mediating inotropic and
electrophysiological effects in mammalian myocardium.
Nagashima, Masato, Yuichi Hattori, Yasuhiro Akaishi, Noritsugu Tohse,
Ichiro Sakuma, Akira Kitabatake, and Morio Kanno.
Departments of Pharmacology and Cardiovascular Medicine Hokkaido
University School of Medicine Sapporo 060, Japan
APStracts 3:0142H, 1996.
Stimulation of FE1-adrenoceptors produces a positive inotropic effect
in rat and rabbit ventricular myocardium via different mechanisms:
the prolongation of action potential duration (APD) exclusively in
the former and an increase in myofibrillar Ca2+ sensitivity in large
part in the latter. This study was designed to determine whether the
two inotropic mechanisms are mediated by different FE1-adrenoceptor
subtypes. In rat papillary muscles, the positive inotropic effect and
APD prolongation induced by phenylephrine (in the presence of
propranolol) were inhibited by WB4101, but not affected by
chlorethylclonidine (CEC). WB4101, but not CEC, blocked the
phenylephrine-induced inhibition of the transient outward current
(Ito) in rat ventricular cells. On the other hand, WB4101 and CEC
each antagonized the positive inotropic effect of phenylephrine in
rabbit papillary muscles. However, the phenylephrine-induced APD
prolongation observed in rabbit papillary muscles was blocked only by
WB4101. These results indicate that the WB4101-sensitive FE1
-adrenoceptor subtype mediates the positive inotropism which is
correlated with the APD prolongation resulting from Ito reduction,
while the CEC-sensitive subtype mediates the positive inotropism
which is probably associated with the increased myofibrillar Ca2+
sensitivity. The radioligand binding studies with [3H]prazosin showed
a similar ratio of FE1A/FE1B-adrenoceptor subtypes in rat and rabbit
ventricular myocardium, implying that the different degree of
contribution of each action mechanism to the overall inotropic effect
in the two species cannot be explained by distribution of the FE1
-adrenoceptor subtypes.
Received 8 May 1995; accepted in final form 15 March 1996.
APS Manuscript Number H437-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96