Pharmacological characterization of alpha-2 adrenergic receptor subtype involved in the release of insulin from isolated rat pancreatic islets.
Alpha-2 adrenoceptors are involved in the inhibition of insulin release induced by sympathetic nerve stimulation. To test the possibility that one of the postulated subtypes of alpha-2 adrenoceptors is differentially implicated in the inhibition of insulin release, we compared the effects of several agonists and antagonists with preferential selectivity for the alpha-2 adrenoceptor subtypes on the release of insulin induced by glucose in rat isolated islets. Similar to the inhibition of glucose-evoked release of insulin by the alpha-2 agonist (nonsubtype selective) UK 14.304, the alpha-2A preferential agonist oxymetazoline, concentration-dependently inhibited the release of insulin. Glucose-evoked insulin release was similarly inhibited by other alpha-2 adrenoceptor agonists such as clonidine, p-aminoclonidine, epinephrine and norepinephrine. However, neither the alpha-1 selective agonist cirazoline, nor the beta adrenoceptor agonist isoproterenol affected glucose-evoked insulin release, thus suggesting that this inhibitory effect is mediated by alpha-2 adrenoceptors, possibly of the alpha-2A subtype. The inhibition of glucose-evoked insulin release induced by the alpha-2 adrenoceptor agonists was concentration-dependently inhibited by the alpha-2 antagonists yohimbine, phentolamine, rauwolscine and idazoxan. However, neither the alpha-1 selective antagonist prazosin, nor the beta selective antagonist propranolol attenuated the inhibition of insulin release induced by alpha-2 adrenoceptor agonists. Furthermore, the inhibition of insulin release induced by UK 14.304 was concentration-dependently antagonized by the alpha-2A preferential antagonist WB-4101.(ABSTRACT TRUNCATED AT 250 WORDS)
Niddam
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Department of Biology, Synthélabo Recherche (Laboratories d'Etudes et de Recherches Synthélabo), Paris, France.
Angel
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Bidet
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Langer
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D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004347:Drug Interactions; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007328:Insulin; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D010109:Oxymetazoline