Electrophysiological evidence for different release mechanism of ATP and NO as inhibitory NANC transmitters in guinea-pig colon.
1. The effect of the P2-purinoceptor antagonist, suramin, the specific N-type voltage-dependent calcium channel blocker, omega-conotoxin GVIA (omega-CgTx) and the delta-opioid receptor agonist [D-Pen2,D-Pen5] enkephalin (DPDPE) on the apamin-sensitive and apamin-resistant inhibitory junction potentials (i.j.ps) produced by electrical field stimulation (EFS) were investigated by means of a sucrose-gap technique in the circular muscle of the guinea-pig colon. 2. After incubation of muscle strips in either atropine (1 microM), guanethidine (3 microM) and NG-nitro-L-arginine (L-NOARG, 30 microM) or atropine, guanethidine and apamin (0.3 microM), the addition of the NK1 receptor antagonist, SR 140,333 (1 microM) abolished the non-adrenergic, non-cholinergic (NANC) excitatory junction potential (e.j.p.) and unmasked a pure apamin-sensitive i.j.p. (in the presence of L-NOARG) or a pure apamin-resistant i.j.p. (in the presence of apamin). Both types of i.j.p. were abolished by tetrodotoxin. 3. Suramin (30-300 microM) concentration-dependently inhibited the apamin-sensitive i.j.p., while the apamin-resistant i.j.p. was not significantly affected by suramin (up to 300 microM). L-NOARG (30 microM) markedly reduced the apamin-resistant i.j.p. 4. The delta-opioid receptor agonist, DPDPE (0.03-3 microM) concentration-dependently reduced the apamin-sensitive i.j.p., while leaving the apamin-resistant i.j.p. unaffected. Naloxone (1 microM) prevented the i.j.p. inhibition evoked by DPDPE (0.3 microM). 5. omega-CgTx (0.3 microM) markedly reduced the apamin-sensitive but not the apamin-resistant i.j.p. The application of DPDPE (3 MicroM), after development of a steady state inhibitory effect by omega-CgTx, evoked further inhibition of the apamin-sensitive ij.p., similar to the effect produced by DPDPE alone. The L-type calcium channel blocker, nifedipine (1 MicroM) did not significantly affect either the apamin-sensitive or the apamin-resistant ij.ps.6. These findings support the purinergic origin of the fast, apamin-sensitive ij.p. produced by EFS in the circular muscle of the guinea-pig colon and strongly suggest that the apamin-sensitive and the apamin-resistant components of the evoked ij.p. utilize different mechanisms for the secretion of theNANC transmitters, ATP and NO, respectively.
Zagorodnyuk
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Department of Neuro-muscular Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Maggi
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D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000502:physiology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009433:Neural Inhibition; D018377:Neurotransmitter Agents / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010455:Peptides / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D004745:Enkephalins; D018377:Neurotransmitter Agents; D010455:Peptides; D019335:Nitroarginine; D001030:Apamin; D009569:Nitric Oxide; D013498:Suramin; D020881:Enkephalin, D-Penicillamine (2,5)-; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; D001120:Arginine