α1B-Adrenoceptor-mediated stimulation of Ca2+ mobilization and cAMP accumulation in isolated rat hepatocytes

Takahide Nomura, Haruhito Kondo, Seiko Hasegawa, Toshiko Watanabe, Rie Yokoyama, Kikuko Ukai, Masakatsu Tachibana, Chiho Ichinose, Hiroko Nomura, Yasumichi Hagino

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Abstract

Noradrenaline stimulates not only Ca2+ mobilization but also cAMP formation through activation of α1-adrenoceptors in hepatocytes from mature male rats. We examined which subtype(s) of α1-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 α1-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 α1B-adrenoceptors are linked to cAMP formation as well as Ca2+ mobilization.

Original languageEnglish
Pages (from-to)113-120
Number of pages8
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume246
Issue number2
DOIs
Publication statusPublished - 15-07-1993

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Adrenergic Receptors
Hepatocytes
Norepinephrine
Prazosin
Pertussis Toxin
Phorbol Esters
Adrenergic Agents
Signal Transduction
Neoplasms
chlorethylclonidine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nomura, Takahide ; Kondo, Haruhito ; Hasegawa, Seiko ; Watanabe, Toshiko ; Yokoyama, Rie ; Ukai, Kikuko ; Tachibana, Masakatsu ; Ichinose, Chiho ; Nomura, Hiroko ; Hagino, Yasumichi. / α1B-Adrenoceptor-mediated stimulation of Ca2+ mobilization and cAMP accumulation in isolated rat hepatocytes. In: European Journal of Pharmacology: Molecular Pharmacology. 1993 ; Vol. 246, No. 2. pp. 113-120.
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α1B-Adrenoceptor-mediated stimulation of Ca2+ mobilization and cAMP accumulation in isolated rat hepatocytes. / Nomura, Takahide; Kondo, Haruhito; Hasegawa, Seiko; Watanabe, Toshiko; Yokoyama, Rie; Ukai, Kikuko; Tachibana, Masakatsu; Ichinose, Chiho; Nomura, Hiroko; Hagino, Yasumichi.

In: European Journal of Pharmacology: Molecular Pharmacology, Vol. 246, No. 2, 15.07.1993, p. 113-120.

Research output: Contribution to journalArticle

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AU - Nomura, Takahide

AU - Kondo, Haruhito

AU - Hasegawa, Seiko

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AU - Yokoyama, Rie

AU - Ukai, Kikuko

AU - Tachibana, Masakatsu

AU - Ichinose, Chiho

AU - Nomura, Hiroko

AU - Hagino, Yasumichi

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N2 - Noradrenaline stimulates not only Ca2+ mobilization but also cAMP formation through activation of α1-adrenoceptors in hepatocytes from mature male rats. We examined which subtype(s) of α1-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 α1-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 α1B-adrenoceptors are linked to cAMP formation as well as Ca2+ mobilization.

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