Postsynaptic alpha-2 adrenergic receptors in isolated rat islets of Langerhans: inhibition of insulin release and cyclic 3':5'-adenosine monophosphate accumulation.

Effects of various alpha adrenergic agents on insulin release and cyclic 3':5'-adenosine monophosphate (cAMP) accumulation in pancreatic islets were investigated. Clonidine, epinephrine, alpha-methylnorepinephrine and norepinephrine were most potent and methoxamine and phenylephrine least potent in inhibiting the glucose-stimulated insulin release. Yohimbine and phentolamine were the most effective and prazosin was the least effective in antagonizing the epinephrine-inhibited insulin release. Clonidine markedly inhibited the glucagon-stimulated cAMP accumulation, whereas methoxamine showed weak inhibition. Yohimbine markedly increased cAMP accumulation in the presence of epinephrine, whereas prazosin showed little effect. The effects of alpha adrenergic agents on rabbit aorta contraction were also examined for comparison with alpha adrenergic receptors in pancreatic islets. In the aorta, the order of agonist potency was norepinephrine greater than phenylephrine greater than epinephrine greater than methoxamine greater than alpha-methylnorepinephrine and that of antagonist potency was prazosin greater than WB-4101 greater than phentolamine greater than dihydroergotamine greater than phenoxybenzamine greater than yohimbine. These orders of potencies were markedly different from those in pancreatic islets. These results clearly demonstrate that the alpha adrenergic receptors in rat pancreatic islets are different from those on rabbit aorta (alpha-1) and are typical postsynaptic alpha-2 adrenergic receptors.