Inhibitory pathways in the circular muscle of rat jejunum.
1. Conflicting data have been reported on the contribution of nitric oxide (NO) to inhibitory neurotransmission in rat jejunum. Therefore, the mechanism of relaxation and contribution to inhibitory neurotransmission of NO, adenosine 5'-triphosphate (ATP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) was examined in the circular muscle of Wistar-Han rat jejunum. 2. Mucosa-free circular muscle strips were precontracted with methacholine in the presence of guanethidine and exposed to electrical field stimulation (EFS) and exogenous NO, ATP, VIP and PACAP. All stimuli induced reduction of tone and inhibition of phasic motility. Only electrically induced responses were sensitive to tetrodotoxin (3 x 10(-6) m). 3. NO (10(-6)-10(-4) m)-induced concentration-dependent relaxations that were inhibited by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ; 10(-5) m) and the small conductance Ca(2+)-activated K(+)-channel blocker apamin (APA; 3 x 10(-8) m). 4. Relaxations elicited by exogenous ATP (10(-4)-10(-3) m) were inhibited by the P2Y purinoceptor antagonist reactive blue 2 (RB2; 3 x 10(-4) m), but not by APA and ODQ. 5. The inhibitory responses evoked by 10(-7) m VIP and 3 x 10(-8) m PACAP were decreased by the selective PAC(1) receptor antagonist PACAP(6-38) (3 x 10(-6) m) and APA. The VPAC(2) receptor antagonist PG99-465 (3 x 10(-7) m) reduced relaxations caused by VIP, but not those by PACAP, while the VPAC(1) receptor antagonist PG97-269 (3 x 10(-7) m) had no influence. 6. EFS-induced relaxations were inhibited by the NO-synthase inhibitor N(omega)-nitro-l-arginine methyl ester (3 x 10(-4) m), ODQ and APA, but not by RB2, PG97-269, PG99-465 and PACAP(6-38). 7. These results suggest that NO is the main inhibitory neurotransmitter in the circular muscle of Wistar-Han rat jejunum acting through a rise in cyclic guanosine monophosphate levels and activation of small conductance Ca(2+)-dependent K(+) channels.
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Gwen
G
Vanneste
Patrick
P
Robberecht
Romain A
RA
Lefebvre
D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects*; D006152:Cyclic GMP / Q000502:physiology; D004558:Electric Stimulation; D007537:Isometric Contraction / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects* / Q000294:innervation; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D051640:Small-Conductance Calcium-Activated Potassium Channels; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D018721:Muscarinic Agonists; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D016210:Methacholine Chloride; D001030:Apamin; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; D006152:Cyclic GMP