THE ROLE OF CGRP AND AFFERENT NERVES IN THE MODULATION OF PANCREATIC-ENZYME SECRETION IN THE RAT

Conclusion. Stimulation of pancreatic sensory nerves by capsaicin prod uced secretory effects probably caused, at least in part, by the relea se of CGRP. Background. In the pancreas calcitonin gene-related peptid e (CGRP) has been localized in the sensory nerves, but its physiologic al role is unknown. This study was undertaken to compare the changes o f pancreatic enzyme secretion produced by CGRP and by stimulation or d estruction of sensory nerves. Methods. To stimulate sensory nerves, lo w doses of capsaicin (0.25-0.5 mg/kg) were given intraduodenally to th e conscious rats with chronic pancreatic fistula. To inactivate sensor y nerves high doses of capsaicin (100 mg/kg) were given subcutaneously 10 d before tests. For the in vitro experiments pancreatic slices and isolated pancreatic acini were prepared from intact and capsaicin-den ervated rats. Results. In conscious rats, CGRP given subcutaneously (5 -10 mu g/kg) and low doses of capsaicin given intraduodenally reduced basal pancreatic secretion. In isolated pancreatic acini, CGRP (10(-10 )-10(-6) M), but not capsaicin, increased basal or secretagog-stimulat ed amylase release. In pancreatic slices (containing nerve fibers) cap saicin (10(-10)-10(-6) M) increased enzyme secretion, and this secreti on was abolished by previous inactivation of sensory nerves by this ne urotoxin. Capsaicin deactivation did not affect the secretory response of pancreatic acini to CGRP, cerulein, or urecholine. Sensory denerva tion by capsaicin did not change basal protein secretion, but reduced that produced by feeding or diversion of pancreatic juice to the exter ior during first 2 h of the tests.