Mediators of non-adrenergic non-cholinergic inhibitory neurotransmission in porcine jejunum.

The purpose of this study was to determine the non-adrenergic non-cholinergic inhibitory neurotransmitter in pig jejunum. Intracellular electrical activity was recorded from circular smooth muscle cells. Inhibitory junction potentials (IJPs) evoked by electrical field stimulation were inhibited by tetrodotoxin (1 micromol L(-1)), omega-conotoxin GVIA (0.1 micromol L(-1)) tetrodotoxin, apamin (1 micromol L(-1)), 1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U-73122; 10 micromol L(-1)) but not by N omega-nitro-l-arginine (l-NNA; 100 micromol L(-1)), haemoglobin (10 micromol L(-1)), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 micromol L(-1)) or 9-(tetrahydro-2-furyl)adenine (SQ-22536; 10 micromol L(-1)). S-nitroso-N-acetylpenicillamine (SNAP) hyperpolarized the membrane potential. This was inhibited by ODQ (3 micromol L(-1)) and charybdotoxin (0.1 micromol L(-1)). Adenosine-5-triphosphate (ATP; 100 micromol L(-1)) and 2-methylthio ATP (2-MeS-ATP; 100 micromol L(-1)) did not hyperpolarize the membrane potential and 6-N-N-diethyl-beta- gamma -dibromomethylene-d-adenosine-5'-triphosphate (ARL67156; 100 micromol L(-1)) did not modify IJPs. Carbon monoxide (CO; 10%) and tricarbonyl dichlororuthenium dimer ([Ru(CO3Cl2)]2; 100 micromol L(-1)) hyperpolarized the membrane potential however zinc, copper and tin protoporphyrin IX (100 micromol L(-1)) did not alter IJPs. Vasoactive intestinal peptide (VIP) hyperpolarized the membrane potential but 4-Cl-d-Phe6-Leu17-VIP (1 micromol L(-1)) did not modify IJPs. Pituitary adenylate cyclase activating peptide (PACAP)38 (0.5 micromol L(-1)) hyperpolarized the membrane potential. This was inhibited by apamin (1 micromol L(-1)) but not by tetrodotoxin (1 micromol L(-1)). Pituitary adenylate cyclase activating peptide6-38 (1 micromol L(-1)) inhibited IJPs. These data suggest that inhibitory neurotransmission in pig jejunum is mediated partly by PACAP.