Investigation of the interaction between cholinergic and nitrergic neurotransmission in the pig gastric fundus

• Published in: British journal of pharmacology Vol. 125; no. 8; pp. 1779 - 1787
• Main Authors: Leclere, P. G., Lefebvre, R. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1998; Nature Publishing
• Subjects: Acetylcholine - pharmacology; Animals; Atropine - pharmacology; Biological and medical sciences; cholinergic; Cholinergic Agents - pharmacology; Chymotrypsin - pharmacology; Electric Stimulation; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; gastric fundus; Gastric Fundus - drug effects; Gastric Fundus - innervation; Gastric Fundus - physiology; Hexamethonium - pharmacology; In Vitro Techniques; interaction; Male; Muscarinic Antagonists - pharmacology; Muscle Contraction - drug effects; Muscle Tonus - drug effects; Muscle Tonus - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nicotinic Antagonists - pharmacology; nitrergic; Nitric Oxide - pharmacology; Nitroprusside - pharmacology; Physostigmine - pharmacology; pig; Serotonin - pharmacology; Stomach; Swine; Synaptic Transmission - drug effects; Tetrodotoxin - pharmacology; Vasodilator Agents - pharmacology; Vertebrates: digestive system; Stomach; Digestive system; Non adrenergic non cholinergic transmission; Smooth muscle; Muscle contraction; In vitro; Pig; Vertebrata; Mammalia; Autonomic nervous system; Animal; Nitric oxide; Neurotransmitter; Gastric fundus; Acetylcholine; Artiodactyla; Ungulata; Cholinergic transmission
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702244

The interaction between the cholinergic and nitrergic innervation was investigated in circular muscle strips of the pig gastric fundus. In physiological salt solution containing 4×10−6 M guanethidine, electrical field stimulation (EFS; 40 V, 0.5 ms, 0.5–32 Hz, 10 s at 4 min intervals) induced small transient relaxations at 0.5–4 Hz, and large frequency‐dependent contractions, sometimes followed by off‐relaxations, at 8–32 Hz. In the presence of L‐NG‐nitroarginine methyl ester (L‐NAME; 3×10−4 M) or physostigmine (10−6 M), relaxations were reversed into contractions and contractions were enhanced. Physostigmine added to L‐NAME further enhanced contractions, while addition of L‐NAME to physostigmine had no additional effect. Off‐relaxations were enhanced in the presence of L‐NAME and physostigmine. L‐NAME and physostigmine consistently increased basal tone. Tissues contracted by 5‐hydroxytryptamine or by acetylcholine responded to EFS in a similar way as in basal conditions and L‐NAME reversed the relaxations at the lower stimulation frequencies into contractions and enhanced the contractions at the higher stimulation frequencies. Off‐relaxations in the presence of L‐NAME were partially reduced by α‐chymotrypsin (10 U ml−1). In the absence of physostigmine, the concentration‐response curve to exogenous acetylcholine was not influenced by L‐NAME. Contractions of the same amplitude induced by EFS at 4 Hz and by exogenous acetylcholine were either decreased or enhanced to the same extent by sodium nitroprusside (SNP; 10−5 M), depending upon the degree of relaxation by SNP. These experiments suggest that endogenous nitric oxide interferes with cholinergic neurotransmission in the pig gastric fundus by functional antagonism at the postjunctional level. The interaction is independent of the degree of contraction.