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.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004285:Dogs; D005947:Glucose / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D007473:Ion Channels; D013779:Tetrodotoxin; D013004:Somatostatin; D014701:Veratridine; D012964:Sodium; D005947:Glucose; D002118:Calcium