Nitric oxide involvement in the peptide VIP-associated inhibitory junction potential in the guinea-pig ileum.
1. Intracellular membrane potential recordings were made from circular smooth muscle cells of the guinea-pig ileum in the presence of atropine (1 microM) and nifedipine (0.1 microM) at 30 degrees C. 2. Electrical field stimulation with one or four pulses produced a fast inhibitory junction potential (IJP) which lasted around 1 s. It was abolished by tetrodotoxin (1 microM), apamin (0.3 microM), and alpha, beta-methylene ATP tachyphylaxis. 3. Nitric oxide synthase inhibitor N-nitro-L-arginine (L-NNA; 200 microM) had no effect on the resting membrane potential or the fast IJP. 4. Electrical field stimulation in the presence of apamin and substance P desensitization produced a slow IJP which was abolished by tetrodotoxin (1 microM). 5. L-NNA significantly reduced the amplitude of the slow IJP (P < 0.01). The antagonistic effect of L-NNA was reversed by L-arginine but not by D-arginine. 6. Injections of alpha, beta-methylene ATP, nitric oxide (NO), and vasoactive intestinal polypeptide (VIP) into the recording chamber caused tetrodotoxin-resistant hyperpolarizations of the smooth muscle membrane. Substance P desensitization did not modify the amplitudes of the hyperpolarizing response to ATP or NO, but increased the VIP hyperpolarization by 150% (P < 0.01). 7. L-NNA did not modify the amplitude of hyperpolarization due to ATP or NO; however, it antagonized VIP-induced hyperpolarization (P < 0.01). 8. These studies show that in the guinea-pig ileum circular muscle: (a) NO is not involved in the fast IJP which is mediated by ATP; (b) NO is involved in the slow IJP which is mediated by VIP and NO acting in series, and (c) the hyperpolarizing effects of VIP and the slow IJP are normally masked by overlapping depolarization due to concomitant release of substance P by the peptide VIP.
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Center for Swallowing and Motility Disorders, Harvard-Thorndike Laboratory, Charles A. Dana Research Institute, Department of Medicine, Boston, MA 02215.
Goyal
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D046508:Culture Techniques; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*
D018377:Neurotransmitter Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001285:Atropine; D001120:Arginine; D009543:Nifedipine