Studies on the Mechanism of Action of Somatostatin on the Endocrine Pancreas. I. Interaction with a-Adrenergic Receptors*

To determine whether inhibition of insulin release by somatostatin (SRIF) might be mediated through aadrenergic receptors, the interaction of the competitive a-adrenergic antagonist phentolamine with SRIF on arginine-stimulated insulin release from rat pancreases perfused in vitro was examined. Phentolamine, at a concentration (5 μM) which completely reversed inhibition of insulin release by 0.05 /IM epinephrine, had no effect on inhibition of insulin release due to 0.05 /xM SRIF; insulin release at comparable periods of arginine stimulation averaged 366 ± 48 ng in control studies, 420 ± 81 ng during infusion of epinephrine plus phentolamine, and 72 ± 12 ng during infusion of SRIF plus phentolamine (P < 0.001). Phentolamine (50 μM) increased insulin release during infusion of SRIF (0.05 JLIM) to values (339 ± 66 ng) not significantly different from those observed in control studies. However, this concentration of phentolamine was found to augment insulin release (600 ± 75 vs. 366 ± 48 ng in control studies; P < 0.01) in the absence of SRIF. To determine whether the apparent reversal of SRIF-induced inhibition of insulin secretion by 50 /IM phentolamine was due to mere augmentation of insulin rather than interaction of phentolamine with SRIF at a-adrenergic receptors, SRIF (0.05 JUM) was infused during augmentation of insulin release by 50 JUM phentolamine. SRIF not only decreased phentolamine-induced augmentation of insulin release (insulin release during phentolamine plus SRIF averaged 285 ± 72 ng compared to 600 ± 75 ng during phentolamine alone; P < 0.01) but also suppressed perfusate insulin levels to values (7–8 ng/ml) lower than those observed in control studies (12-15 ng/ml; P < 0.05). Thus, since phentolamine at a concentration which reversed epinephrine-induced inhibition of insulin did not reverse SRIF-induced inhibition of insulin release and since augmentation of insulin release by phentolamine was itself inhibited by SRIF, it seems unlikely that SRIF inhibits insulin release through activation of islet a-adrenergic receptors.