α1-Adrenoceptor-mediated Ca2+-entry from the extracellular fluid and Ca2+-release from intracellular stores: No role for α(1A,B)-adrenoceptor subtypes in the pithed rat

Schwietert, H. R., Mathy, M-J., Wilhelm, D., Wilffert, B., Pfaffendorf, M. & Van Zwieten, P. A., 22-Oct-1992, In : Journal of autonomic pharmacology. 12, 3, p. 125-136 12 p.

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  • H.R. Schwietert
  • M.-J. Mathy
  • D. Wilhelm
  • B. Wilffert
  • M. Pfaffendorf
  • P.A. Van Zwieten
1. In the present study, we tested the hypothesis that in the pithed rat preparation two subtypes of the α1-adrenoceptor are linked to two different signal transduction mechanisms, both of which contribute to vasoconstriction, one facilitating Ca2+-entry from the extracellular fluid (α(1A)) and one promoting the release of Ca2+from intracellular sources (α(1B)). 2. The selective α(1A)-adrenoceptor antagonist, 5-methyl-urapidil, and the selective α(1B)-adrenoceptor antagonist, chloroethylclonidine, were unable to discriminate between α1-adrenoceptor-mediated pressor responses, which relied on an entry of extracellular Ca2+sensitive to nifedipine and an intracellular release of Ca2+insensitive to nifedipine, respectively. 3. Chloroethylclonidine, 12.5 and 25 mg kg-1i.v., were equieffective, and had only minor effects on α1-adrenoceptor-mediated increases in diastolic blood pressure. This could be associated with a small decrease in the receptor-reserve of the pithed rat preparation due to irreversible receptor blockade by this antagonist. These data indicate that chloroethylclonidine-sensitive α1-adrenoceptors constitute only a minor fraction of the total α1-adrenoceptor population on rat arterial resistance vessels. 4. Chloroethylclonidine behaved as a partial agonist eliciting a small increase in baseline diastolic blood pressure which could be inhibited by Ca2+-entry blockade with nifedipine. 5. Chloroethylclonidine potentiated the pressor responses elicited by the α2-adrenoceptor agonists UK-14,304 and azepexole (B-HT 933). 6. No evidence was found in the pithed rat that α1-adrenoceptor-mediated Ca2+-entry from the extracellular fluid and Ca2+-release from intracellular stores are mediated by α(1A) and α(1B)-adrenoceptors, respectively.
Original languageEnglish
Pages (from-to)125-136
Number of pages12
JournalJournal of autonomic pharmacology
Issue number3
Publication statusPublished - 22-Oct-1992


  • 5 methylurapidil, adrenergic receptor, azepexole, brimonidine, chloroethylclonidine, cirazoline, indanidine, nifedipine, prazosin, yohimbine, animal experiment, article, blood pressure, calcium cell level, controlled study, intravenous drug administration, ion transport, male, nonhuman, rat

ID: 14126172