ALPHA-1-ADRENOCEPTOR-MEDIATED CA2+-ENTRY FROM THE EXTRACELLULAR FLUID AND CA2+-RELEASE FROM INTRACELLULAR STORES - NO ROLE FOR ALPHA-1A,B-ADRENOCEPTOR SUBTYPES IN THE PITHED RATSCHWIETERT, HR., MATHY, MJ., WILHELM, D., WILFFERT, B., PFAFFENDORF, M. & VANZWIETEN, PA., Jun-1992, In : Journal of autonomic pharmacology. 12, 3, p. 125-136 12 p.
Research output: Contribution to journal › Article › Academic › peer-review
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 Ca2+-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 Ca2+-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 Ca2+-entry from the extracellular fluid and Ca2+-release from intracellular stores are mediated by alpha-1A and alpha-1B-adrenoceptors, respectively.
|Number of pages||12|
|Journal||Journal of autonomic pharmacology|
|Publication status||Published - Jun-1992|
- ALPHA-1-ADRENERGIC RECEPTOR SUBTYPES, INOSITOL PHOSPHATES, PRESSOR-RESPONSES, SMOOTH-MUSCLE, ALPHA-1, ANTAGONISTS, BINDING, BRAIN, CHLORETHYLCLONIDINE, SUBCLASSIFICATION