Role of alpha 1-adrenoceptor subtypes which mediate positive chronotropy in neonatal rat cardiac myocytes.
We investigated the involvement of alpha 1-adrenoceptor subtypes in the positive chronotropic response to norepinephrine (NE) in neonatal rat cardiac myocytes at day 3 of culture. The cardiac myocytes at day 3 of culture exhibited a dose-dependent positive chronotropic response to NE in the presence of propranolol, a beta-adrenoceptor antagonist. The positive chronotropic responses to NE were completely antagonized by the alpha 1-adrenoceptor antagonist prazosin. The NE-induced positive chronotropic response was inhibited 68% by the alpha 1B-adrenoceptor antagonist, chloroethylclonidine (CEC), but partially (41%) so by the alpha 1A-adrenoceptor antagonist, WB4101. In the membrane fraction derived from cardiac myocytes at day 3 of culture, pretreatment with CEC decreased the Bmax of the alpha 1-adrenoceptor to 22% of the control value. The NE-induced positive chronotropic response was inhibited 62 and 77% by the voltage-gated Ca2+ channel blocker such as nifedipine and verapamil, respectively. These findings indicate (1) that cultured neonatal rat cardiac myocytes possess both alpha 1-adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, (2) that the predominant alpha 1-adrenoceptor subtypes mediating NE-induced positive chronotropy in neonatal rat cardiac myocytes at day 3 of culture are alpha 1B-subtypes, and (3) that NE-induced positive chronotropy may be caused via voltage-gated Ca2+ channel activation.
Kimura
H
H
Department of Pharmacology, School of Medicine, Sapporo Medical University, Japan.
Kawana
S
S
Kanaya
N
N
Sakano
S
S
Miyamoto
A
A
Ohshika
H
H
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D006339:Heart Rate / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis / Q000502:physiology*; D013268:Stimulation, Chemical
D015220:Calcium Channels; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine