NANC relaxation of the circular smooth muscle of the oesophagus of the Agama lizard involves the L-arginine-nitric oxide synthase pathway.
On carbachol (CCh; 10-30 microM) pre-contracted circular muscle strips of the Agama lizard oesophagus, electrical field stimulation evoked frequency-dependent relaxations in the presence of guanethidine (1 microM) and indomethacin (1 microM). These non-adrenergic inhibitory responses were concentration-dependently inhibited by the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) within a concentration range of 30-300 microM but not D-NAME (up to 300 microM), although a component remained at 4-16 Hz even with 300 microM L-NAME. The inhibition by L-NAME (300 microM) was completely prevented when L-arginine (L-Arg; 15 mM) but not D-Arg (up to 15 mM) was applied simultaneously with L-NAME (300 microM). Increasing the L-NAME concentration to 1 mM had no additional inhibitory effect. Sodium nitroprusside (SNP) concentration-dependently relaxed pre-contracted oesophageal strips, L-NAME (up to 300 microM) had no effect. Neither adenosine 5'-triphosphate (up to 0.1 mM) nor vasoactive intestinal polypeptide (up to 0.1 microM) caused the pre-contracted oesophagus to relax. This study has shown that the NANC inhibitory response of the Agama lizard oesophagus circular muscle largely involves the L-Arg-NOS pathway as seen by the effect of L-NAME, L-Arg and SNP. The identity of the L-NAME-resistant component(s) and the lack of effect of tetrodotoxin (up to 3 microM) and omega-conotoxin GVIA (up to 0.1 microM) in relation to the nature of the inhibitory response are discussed.
Knight
G E
GE
Autonomic Neuroscience Institute, Royal Free Hospital School of Medicine, London, UK.
Burnstock
G
G
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D004848:Epithelium / Q000502:physiology; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008116:Lizards / Q000502:physiology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D018663:Adrenergic Agents; D010455:Peptides; D009599:Nitroprusside; D013779:Tetrodotoxin; D020866:omega-Conotoxin GVIA; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; D006145:Guanethidine