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The role of α1-adrenoceptor subtypes in the phasic and tonic responses to phenylephrine in the longitudinal smooth muscle of the rat portal vein

Schwietert, H. R., Gouw, M. A. M., Wilhelm, D., Wilffert, B. & Van Zwieten, P. A., 22-Oct-1991, In : Naunyn-Schmiedeberg's Archives of Pharmacology. 343, 5, p. 463-471 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • H.R. Schwietert
  • M.A.M. Gouw
  • D. Wilhelm
  • B. Wilffert
  • P.A. Van Zwieten
The purpose of this investigation was to determine whether α1-adrenoceptor subtypes (co)exist in the rat portal vein and, if so, whether they could be functionally associated with the phasic and tonic types of contraction as a response to α1-adrenoceptor stimulation by phenylephrine. A low Ca2+concentration (0.9 mmol/l) in the Tyrode solution enabled us to quantify changes both in the phasic myogenic activity and in the basal tone of the rat portal vein preparation very precisely. We used both competitive and non-competitive α-adrenoceptor antagonists which have been employed successfully by other investigators to discriminate between α1-adrenoceptor subtypes in vascular and other tissues. Schild analysis showed that the competitive α-adrenoceptor antagonists prazosin, phentolamine, yohimbine, corynanthine, idazoxan, rauwolscine and 5-methyl-urapidil could not distinguish between the phasic and tonic responses to phenylephrine and/or different α1-adrenoceptor subtypes in the rat portal vein. However, when we compared our pA2values with those found to be representative indicators according to subclassifications based on the use of selective antagonists in different tissues, the α1-adrenoceptors in the rat portal vein appeared to belong to the α(1L)- or α(1a)-subtype. This subclassification was not in accordance with the data obtained with the irreversible α-adrenoceptor antagonist chloroethylclonidine. However, the validity of this alkylating agent as a tool for receptor classification was restricted, at least in the rat portal vein, by its effects on receptor reserve. In contrast to the competitive α-adrenoceptor antagonists, the irreversible α-adrenoceptor antagonists phenoxybenzamine and chloroethylclonidine could indeed discriminate between the phasic and tonic types of contraction in response to α1-adrenoceptor stimulation by phenylephrine, indicating two different receptor reserves for phenylephrine for the two types of responses. In conclusion, both the phasic and tonic types of contraction elicited by phenylephrine in the longitudinal smooth muscle of the rat portal vein appear to be mediated by one particular α1-adrenoceptor subtype as defined by Schild analysis with selective, competitive α-adrenoceptor antagonists. However, using the method of receptor alkylation with phenoxybenzamine, two different affinity constants for the two types of responses could be calculated for phenylephrine. This may reflect the involvement of two different subtypes of α1-adrenoceptors or, more probably, the existence of only one α1-adrenoceptor subtype, which is coupled with two different intrinsic efficacies to the effector pathways mediating the phasic and tonic responses, respectively.
Original languageEnglish
Pages (from-to)463-471
Number of pages9
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume343
Issue number5
Publication statusPublished - 22-Oct-1991

    Keywords

  • α1-adrenoceptor subtypes, phasic contraction, phenylephrine, rat portal vein, tonic contraction, 5 methylurapidil, alpha 1 adrenergic receptor, alpha adrenergic receptor blocking agent, chloroethylclonidine, corynanthine, idazoxan, phenoxybenzamine, phentolamine, prazosin, rauwolscine, receptor subtype, yohimbine, animal tissue, article, concentration response, controlled study, extracellular calcium, male, nonhuman, portal vein, priority journal, rat, smooth muscle contractility, smooth muscle tone

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