ALPHA-2 ADRENERGIC AGONISM STIMULATES ISLET GLUCAGON-RELEASE FROM PERFUSED RAT PANCREAS - POSSIBLE INVOLVEMENT OF ALPHA-2A ADRENERGIC-RECEPTOR SUBTYPE

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 < 0.0 1). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10(-6) mol/I affected glucagon release. Further more, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10(-6) and 10(-5) mol/I and the alpha-I 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-I 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.