title: Mediators of non-adrenergic non-cholinergic inhibitory neurotransmission in porcine jejunum.
abstract: 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.
authors.affiliation: Enteric Neuroscience Program, Department of Physiology and Biomedical Engineering, Mayo Clinic, Mayo Clinic, Rochester, MN, USA. nmmatsuda@uol.com.br
authors.forename: N M
authors.initials: NM
authors.lastname: Matsuda
authors.forename: S M
authors.initials: SM
authors.lastname: Miller
authors.forename: L
authors.initials: L
authors.lastname: Sha
authors.forename: G
authors.initials: G
authors.lastname: Farrugia
authors.forename: J H
authors.initials: JH
authors.lastname: Szurszewski
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects / Q000294:innervation*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D020960:omega-Conotoxins; D001030:Apamin; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate