Endogenous vasoactive intestinal peptide and nitric oxide modulate cholinergic neurotransmission in guinea-pig trachea.
Guinea-pig tracheal smooth muscle possesses an inhibitory non-adrenergic, non-cholinergic (i-NANC) innervation and the neurotransmitters involved in this response may be vasoactive intestinal peptide (VIP) and nitric oxide (NO). Since i-NANC mechanisms may co-exist with cholinergic nerves we have investigated whether endogenous VIP and NO modulate cholinergic neurotransmission. alpha-Chymotrypsin enhanced the cholinergic contractile responses to electrical field stimulation (EFS at 4 Hz by 38.6 +/- 4.8% (P < 0.05, n = 6) but did not produce a shift in the concentration-response curve to acetylcholine (ACh). L-NG-Nitro-arginine methyl ester (L-NAME) and L-NG-monomethyl arginine (L-NMMA) produced a concentration-dependent enhancement of cholinergic responses to EFS (4 Hz) (at 100 microM, 40.9 +/- 6.6 and 30.2 +/- 5.8%, P < 0.01) with no effect on response curves to ACh. This enhancement was reversed by L-arginine but not D-arginine (1 mM). D-NAME and D-NMMA and L-arginine had no effect on cholinergic neurotransmission. alpha-Chymotrypsin and L-NAME had no effect on excitatory NANC (e-NANC) neural responses in guinea-pig bronchi. These results suggest that endogenous NO and VIP may modulate cholinergic neurotransmission by either functional antagonism at the level of the airway smooth muscle or via a pre-junctional inhibition of ACh release from cholinergic nerve terminals or by both mechanisms.
Belvisi
M G
MG
Department of Thoracic Medicine, National Heart and Lung Institute, Chelsea, London, UK.
Miura
M
M
Stretton
D
D
Barnes
P J
PJ
D000109:Acetylcholine / Q000502:physiology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000294:innervation; D002918:Chymotrypsin / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002918:Chymotrypsin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester