Selective tachykinin NK3-receptor agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig

The tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK3-tachykinin receptor agonist, and senktide, a synthetic NK3-tachykinin receptor agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10(-10) to 10(-6)M), PG-KII and senktide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5+/-0.8 and 8.1+/-0.6% of the total lobular amylase content) than carbachol (34.4+/-3.9%), caerulein (26.5+/-2.8%) and KCl (22.5+/-3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK3 receptor antagonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10(-7)M) also slightly though significantly increased the response to lower concentrations of caerulein (10(-11) and 10(-10)M) and carbachol (10(-7) and 10(-6)M). These findings show that PG-KII and senktide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK3 receptors, without cholinergic involvement. We suggest also that the tachykininergic NK3 receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion.