scholarly journals Histamine Receptors Mediating a Positive Inotropic Effect in Guinea Pig and Rabbit Ventricular Myocardium: Distribution of the Receptors and Their Possible Intracellular Coupling Processes

1994 ◽  
Vol 65 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Yuichi Hattori ◽  
Satoshi Gando ◽  
Masato Nagashima ◽  
Morio Kanno
1996 ◽  
Vol 271 (4) ◽  
pp. H1423-H1432
Author(s):  
M. Nagashima ◽  
Y. Hattori ◽  
Y. Akaishi ◽  
N. Tohse ◽  
I. Sakuma ◽  
...  

Stimulation of alpha 1-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 alpha 1-adrenoceptor subtypes. In rat papillary muscles, the positive inotropic effect and APD prolongation induced by phenylephrine (in the presence of propranolol) were inhibited by WB-4101, but not affected by chlorethylclonidine (CEC). WB-4101, but not CEC, blocked the phenylephrine-induced inhibition of the transient outward current (Ito) in rat ventricular cells. On the other hand, WB-4101 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 WB-4101. These results indicate that the WB-4101 sensitive alpha 1-adrenoceptor subtype mediates the positive inotropism that is correlated with the APD prolongation resulting from Ito reduction, whereas the CEC-sensitive subtype mediates the positive inotropism that is probably associated with increased myofibrillar Ca2+ sensitivity. Radioligand binding studies with [3H] prazosin showed a similar ratio of alpha 1A-to alpha 1B-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 alpha 1-adrenoceptor subtypes.


1991 ◽  
Vol 261 (3) ◽  
pp. H611-H619 ◽  
Author(s):  
M. Takanashi ◽  
M. Endoh

Endothelin-1 elicited a positive inotropic effect (PIE) on isolated rabbit, guinea pig, and rat but not on dog ventricular myocardium. Specific high-affinity binding of 125I-labeled endothelin-1 was detected in the ventricular membrane fraction of these species. Maximal binding capacity was the highest in the rabbit, lowest in the dog, and in between in the guinea pig and rat; this rank order corresponds roughly to the effectiveness of endothelin-1 in producing a PIE. There was no difference in the potency or efficacy for the PIE of the endothelin isoforms endothelin-1, -2, and -3 in the rabbit papillary muscle. A tumor-promoting phorbol ester, phorbol 12,13-dibutyrate, inhibited selectively the PIE and the accumulation of [3H]inositol monophosphate induced by endothelin-1 as well as those of myocardial alpha 1-adrenoceptor stimulation in a concentration that did not (10(-8) M) or only slightly (10(-7) M) reduced the PIE of BAY K 8644. Phorbol 12,13-dibutyrate did not affect the specific binding of 125I-labeled endothelin-1 in the ventricular membrane fraction of the rabbit. The present findings indicate that the characteristics of the endothelin-induced PIE in mammalian ventricular myocardium are similar to those of myocardial alpha 1-adrenoceptor activation that may involve phosphoinositide hydrolysis. The receptor density and the PIE of endothelin on mammalian cardiac muscle show a wide range of variation among species.


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