Substance P inhibits pancreatic exocrine secretion via a neural mechanism

We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancre as. SP inhibited CCK-induced amylase release and secretin-induced juice flo w via the pancreatic duct in a dose-related fashion. Threshold inhibition o ccurred following addition of 10(-10) M SP to the perfusate, and maximal in hibition was seen with 10(-8) M SP. The effects of SP were partially blocke d by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonist s. Atropine and TTX blocked SP-induced effects on both amylase secretion (2 6 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blo ckade, respectively). Excitation of pancreatic sensory nerves using capsaic in tin the absence of SP inhibited both amylase and pancreatic juice flow v ia activation of the NK1 receptor. We conclude that SP inhibits exocrine se cretion via an indirect neural mechanism.