Modulation of pancreatic secretion by capsaicin-sensitive sensory neurons in the rat.

ABSTRACT

The purpose of this work was to study whether stimulation or destruction of sensory afferents can modulate pancreatic secretion. The neurotoxin capsaicin is specific for a subpopulation of small diameter primary afferent neurons. Small doses of capsaicin were administered to anesthetized rats as intraduodenal or intragastric bolus injections to stimulate digestive sensory fibers, and pancreatic secretory response was measured. In addition, several high-dose subcutaneous capsaicin injections were administered 10 days before the experiments began, in order to inactivate sensory fibers. Basal and 2-deoxy-D-glucose (2DG)-stimulated pancreatic secretion was then measured. Intraduodenal capsaicin (96-3,050 micrograms/kg) induced a progressive (peak response 40-60 min after the injection), dose-related and long-lasting (> 180 min) increase in pancreatic output of sodium, bicarbonate, and total protein. The maximal response was obtained with 964 micrograms/kg capsaicin; it amounted to about 15% of the maximal response to exogenous cholecystokinin octapeptide (CCK8). The response was not decreased by atropine, hexamethonium, vagotomy, a mixture of adrenoceptor antagonists (prazosin + idazoxan + propranolol), or by the CCKB receptor antagonist L365,260. In contrast, the CCKA receptor antagonist L364,718 reduced by 30-40% the sodium and bicarbonate response and reduced by 90% the protein response induced by capsaicin, but not the response induced by methacholine or 2DG. However, intraluminal capsaicin did not release CCK in a preparation of isolated perfused duodeno-jejunum. Intragastric capsaicin did not significantly change pancreatic secretion. Capsaicin pretreatment had no effect on basal and 2DG-stimulated secretion, but abolished the response to intraduodenal capsaicin. In conclusion, intraduodenal capsaicin can stimulate external pancreatic secretion in anesthetized rats through capsaicin-sensitive sensory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)