GALANIN MODULATES SPHINCTER OF ODDI FUNCTION IN THE AUSTRALIAN BRUSH-TAILED POSSUM

The neuropeptide galanin (GAL) is found in neurons in the biliary trac t of several species. We mapped the distribution of GAL-like immunorea ctive nerve (GALLI) fibers in the sphincter of Oddi of the Australian brush-tailed possum by immunohistochemistry. The pharmacological effec ts of GAL in vitro and in vivo were studied by measuring sphincter of Oddi muscle strip contractility and transsphincteric flow, respectivel y. Muscle layers, and ganglionated and perivascular plexuses, containe d GAL-LI nerve fibers. Exogenous GAL caused a concentration-dependent (10(-9)-10(-6) M) increase in the spontaneous longitudinal but not cir cular muscle contractions. At 10(-6) M GAL, contractile activity was e levated two- to fourfold. This response was tetrodotoxin insensitive b ut competitively inhibited by galantide (10(-8)-10(-7) M). In vivo, in tra-arterial bolus injections of GAL (100-1000 ng/kg), decreased trans sphincteric flow, with a maximum reduction to 80.2 +/- 6.8% of control . In conclusion, GAL appears to selectively stimulate longitudinally o riented sphincter of Oddi smooth muscle via a direct mechanism, which results in a modest reduction in transsphincteric flow.