Contribution of both alpha- and beta-adrenoceptors to the inotropic effects of catecholamines in the rabbit heart.
The functional role of alpha-adrenoceptors was investigated in different parts of the rabbit heart. Phenylephrine (PE) caused a marked increase in force of contraction (Fc) and a prolongation of the action potential (AP) in preparations from the left atrium and the right ventricle. The response was less pronounced in the right atrium and in the left ventricle, whereas APs of spontaneously beating sinoatrial preparations remained completely unchanged. Phentolamine as well as the diesters phorbol 12,13 dibutyrate (PDBu) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA) eliminated the effects of PE. The contribution of alpha-adrenoceptors to the effects of adrenaline (Adr) and noradrenaline (NA) on Fc was determined in preparations from the right ventricle. Phentolamine and the phorbol diesters reduced the effects of Adr and NA by about 30 to 60%; the remaining response was abolished by propranolol. It can be derived from our experiments that, in some parts of the rabbit heart, a considerable amount of the effects of Adr and NA is due to the stimulation of alpha-adrenoceptors. The present findings therefore support the view that, in the rabbit heart, the maximally effective drive of the heart requires the stimulation of both alpha- and beta-adrenoceptors. The inhibitory effects of phorbol diesters on the alpha-adrenoceptor-mediated response indicate that the activation of protein kinase C (PKC) specifically uncouples alpha-adrenoceptors from the effector system, whereas the response to beta-adrenoceptor stimulation remains unchanged.
Jahnel
U
U
Pharmakologisches Institut, Universität Mainz, Federal Republic of Germany.
Kaufmann
B
B
Rombusch
M
M
Nawrath
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D010703:Phorbol Esters; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine