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 tetrodoto xin (1 μmol L^-1), ω-conotoxin GVIA (0.1 μmol L^-1) tetrodotoxin, apamin (1 μmol L^-1), 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2, 5-dione (U-73122; 10 μmol L^-1) but not by Nω-nitro-L- arginine (L-NNA; 100 μmol L^-1), haemoglobin (10 μmol L ^-1), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μmol L^-1) or 9-(tetrahydio-2-furyl)adenine (SQ-22536; 10 μmol L ^-1). S-nitroso-N-acetylpenicillamine (SNAP) hyperpolarized the membrane potential. This was inhibited by ODQ (3 μmol L^-1) and charybdotoxin (0.1 μmol L^-1). Adenosine-5-triphosphate (ATP; 100 μmol L^-1) and 2-methylthio ATP (2-MeS-ATP; 100 μmol L ^-1) did not hyperpolarize the membrane potential and 6-N-N-diethyl-β-γ-dibromomethylene-D-adenosine-5′-triphosphate (ARL67156-, 100 μmol L^-1) did not modify IJPs. Carbon monoxide (CO; 10%) and tricarbonyl dichlororuthenium dimer ([Ru(CO₃Cl ₂)]₂; 100 μmol L^-1) hyperpolarized the membrane potential however zinc, copper and tin protoporphyrin IX (100 μmol L^-1) did not alter IJPs. Vasoactive intestinal peptide (VIP) hyperpolarized the membrane potential but 4-Cl-D-Phe⁶-Leu ¹⁷-VIP (1 μmol L^-1) did not modify IJPs. Pituitary adenylate cyclase activating peptide (PA-CAP)38 (0.5 μmol L^-1) hyperpolarized the membrane potential. This was inhibited by apamin (1 μmol L^-1) but not by tetrodotoxin (1 μmol L^-1). Pituitary adenylate cyclase activating peptide6-38 (1 μmol L^-1) inhibited IJPs. These data suggest that inhibitory neurotransmission in pig jejunum is mediated partly by PACAP.