Inhibition of the NANC relaxation of the guinea-pig proximal colon longitudinal muscle by the purinoceptor antagonist PPADS, inhibition of nitric oxide synthase, but not by a PACAP/VIP antagonist.
The effects of the P(2)-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl- 2('),4(')- disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor N(G)-nitro- l -arginine (l -NOARG), the K(+)-channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the sensory neuron-blocking drug capsaicin were examined on the non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation in the longitudinal muscle of the guinea-pig proximal colon. Both PPADS (50 microm) and l -NOARG (100 microm) significantly inhibited the NANC relaxation. In the presence of l -NOARG, PPADS inhibited and apamin (100 nm) practically abolished the response. Capsaicin slightly but significantly enhanced the NANC relaxation at 10, but not at 1 Hz stimulation frequency. PACAP(6-38) (3 microm) had no effect on the NANC relaxation, although it abolished the relaxant effect of exogenous PACAP(1-27) (10 nm) and reduced that of exogenous vasoactive intestinal polypeptide (VIP, 30-100 nm) by about 60 %. PPADS (50 microm) inhibited the relaxant action of exogenous adenosine 5(')-triphosphate (ATP; 1 and 10 microm), the inhibition being stronger at 1 microm ATP. These data indicate that an exogenous P(2)-purinoceptor stimulant (possibly ATP) and NO are involved in the NANC relaxation of the guinea-pig colon. The 'non-nitrergic' apamin-sensitive component of the response might also include an unidentified transmitter. No evidence has been found for a mediating role of PACAP/VIP-like peptides.
Rózsai
B
B
Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Pécs, H-7643, Hungary.
Lázár
Z
Z
Benkó
R
R
Barthó
L
L
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009433:Neural Inhibition / Q000187:drug effects; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D018663:Adrenergic Agents; D018678:Cholinergic Agents; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D058919:Purinergic P2 Receptor Antagonists; D014665:Vasodilator Agents; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D014660:Vasoactive Intestinal Peptide; D011732:Pyridoxal Phosphate; D019001:Nitric Oxide Synthase