Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat pancreas: Possible involvement of alpha-2A adrenergic receptor subtype

H. Hirose, H. Maruyama, K. Itoh, K. Koyama, K. Kido, T. Saruta

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10-8 and 10-7 mol/l, respectively (p < 0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10-6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10-6 and 10-5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10-5 mol/l showed significant antagonism of 10-7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10-5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.

Original languageEnglish
Pages (from-to)279-283
Number of pages5
JournalActa Endocrinologica
Volume127
Issue number3
DOIs
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Endocrinology

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