α₁‐adrenoceptor‐mediated Ca²⁺‐entry from the extracellular fluid and Ca²⁺‐release from intracellular stores: no role for α_{1A, B} ‐a drenoceptor subtypes in the pithed rat

Abstract

1. In the present study, we tested the hypothesis that in the pithed rat preparation two subtypes of the alpha 1-adrenoceptor are linked to two different signal transduction mechanisms, both of which contribute to vasoconstriction, one facilitating Ca(2+)-entry from the extracellular fluid (alpha 1A) and one promoting the release of Ca2+ from intracellular sources (alpha 1B). 2. The selective alpha 1A-adrenoceptor antagonist, 5-methyl-urapidil, and the selective alpha 1B-adrenoceptor antagonist, chloroethylclonidine, were unable to discriminate between alpha 1-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-1 i.v., were equieffective, and had only minor effects on alpha 1-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 alpha 1-adrenoceptors constitute only a minor fraction of the total alpha 1-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 Ca(2+)-entry blockade with nifedipine. 5. Chloroethylclonidine potentiated the pressor responses elicited by the alpha 2-adrenoceptor agonists UK-14,304 and azepexole (B-HT 933). 6. No evidence was found in the pithed rat that alpha 1-adrenoceptor-mediated Ca(2+)-entry from the extracellular fluid and Ca(2+)-release from intracellular stores are mediated by alpha 1A and alpha 1B-adrenoceptors, respectively.