The role of sodium in somatostatin secretion: evidence for the involvement of Na+ channels in the release mechanism.

The influence of Na+ upon the secretion of somatostatin from the isolated perfused canine pancreas was studied. The Na+ channel-opening alkaloid veratridine (10 microM) was found to cause a biphasic increase in somatostatin output as a normal Ca++ concentration of 1.3 mM. The response to veratridine was inhibited 70% by the addition of 1 microM tetrodotoxin (TTX) and was totally abolished in the absence of extracellular Ca++. TTX (1 microM) reversibly inhibited (by 30%) the glucose-induced somatostatin secretion. During Ca++ depletion, the inhibitory effect of TTX was eliminated. Partial replacement of extracellular Na+ by choline (40 mM Na+ and 100 mM choline) caused a 3- to 4-fold increase in somatostatin secretion. This finding and the fact that the somatostatin response to Na+ withdrawal required the presence of extracellular Ca++ suggest that the stimulatory effect of a decrease in extracellular Na+ concentration is mediated, at least in part, by a Na+-Ca++ countertransport mechanism. The results indicate that the Na+-mediated somatostatin release is dependent upon the extracellular Ca++ concentration. It is unlikely that Na+ per se or via redistribution of the intracellularly bound Ca++ can stimulate somatostatin secretion.