Effect and mechanism of vagal nerve stimulation on somatostatin secretion in dogs

To investigate the effect of vagal nerve stimulation on the release of pancreatic somatostatin, we electrically stimulated (10 Hz, 5 ms, 13.5 mA, and 10 min) the thoracic vagi just below the heart in halothane anesthetized dogs (n = 15). The stimulation increased the pancreatic output of somatostatinlike immunoreactivity (SLI) (delta = +248 +/- 81 fmol/min, P less than 0.005; base-line levels = 455 +/- 150 fmol/min). min). Arterial plasma SLI levels increased as well (delta = +16 +/- 3 fmol/ml, P less than 0.001; base-line levels = 65 +/- 3 fmol/ml), reflecting stimulation of extrapancreatic SLI secretion. Significant vagal activation was verified by a fivefold increase of pancreatic output of pancreatic polypeptide (PP) (delta = +31.4 +/- 5.9 ng/min, P less than 0.001; base-line levels = 7.8 +/- 0.9 ng/min). Atropine pretreatment (n = 6) inhibited partially both the PP response (delta = +7.9 +/- 3.8 ng/min after atropine) and the pancreatic SLI response (delta = +92 +/- 29 fmol/min) to vagal nerve stimulation. However, atropine pretreatment did not modify the arterial SLI response (delta = +20 +/- 7 fmol/ml). Hexamethonium pretreatment (n = 9) completely abolished all three responses. We conclude that 1) electrical stimulation of the vagus stimulates pancreatic SLI, extrapancreatic SLI, and PP release in vivo in the dog; 2) both muscarinic and nonmuscarinic mechanisms mediate the PP and pancreatic SLI responses; 3) a nonmuscarinic mechanism mediates the extrapancreatic SLI response; and 4) all three responses are mediated via ganglionic nicotinic receptors.