Alpha 1B-adrenoceptor-mediated stimulation of Ca2+ mobilization and cAMP accumulation in isolated rat hepatocytes.
Noradrenaline stimulates not only Ca2+ mobilization but also cAMP formation through activation of alpha 1-adrenoceptors in hepatocytes from mature male rats. We examined which subtype(s) of alpha 1-adrenoceptor mediate these signal transduction mechanisms. Treatment of hepatocytes with chloroethylclonidine produced a dose-dependent inhibition of noradrenaline-induced Ca2+ mobilization, involving both transient and sustained components. Chloroethylclonidine also blocked noradrenaline-induced cAMP accumulation. It was observed that prazosin was much more potent than WB4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane) in antagonizing noradrenaline-induced Ca2+ mobilization. The same potency order was found in cAMP formation studies. Pretreatment of rats with pertussis toxin did not affect alpha 1-adrenergic responsiveness. Incubations of hepatocytes with tumor-promoting phorbol esters eliminated both Ca2+ mobilization and cAMP accumulation caused by noradrenaline. Our data suggest that in hepatocytes from mature male rats, single alpha 1B-adrenoceptors are linked to cAMP formation as well as Ca2+ mobilization.
Nomura
T
T
Department of Pharmacology, Fujita Health University School of Medicine, Aichi, Japan.
Kondo
H
H
Hasegawa
S
S
Watanabe
T
T
Yokoyama
R
R
Ukai
K
K
Tachibana
M
M
Sumi-Ichinose
C
C
Nomura
H
H
Hagino
Y
Y
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004146:Dioxanes / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D010656:Phenylephrine; C051731:chlorethylclonidine; D000242:Cyclic AMP; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D037342:Pertussis Toxin; D008729:Methoxamine; D003000:Clonidine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin