Biphasic effect of SNP on opossum esophageal longitudinal muscle: involvement of cGMP and eicosanoids.
Effects of nitric oxide (NO)-containing compounds on opossum esophageal longitudinal smooth muscle in vitro were examined. Sodium nitroprusside (SNP) and authentic NO produced a biphasic concentration-dependent relaxation-contraction sequence in the esophageal longitudinal muscle (ELM) but only a concentration-dependent relaxation of the lower esophageal sphincter (LES) and no effect in the esophageal circular muscle. A cell membrane-permeable analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) also produced relaxation-contraction sequence in the ELM and relaxation of the LES. The guanylate cyclase inhibitors methylene blue (MB) and LY-83583 increased resting tone and had no significant effect on SNP-induced relaxation of ELM. However, they abolished the SNP- and NO-induced contraction of ELM. The cyclooxygenase inhibitor indomethacin had no effect on ELM relaxation and abolished the contractions due to SNP, NO, and 8-BrcGMP. These studies show that in the ELM 1) SNP, authentic NO, and 8-BrcGMP cause a biphasic relaxation-contraction sequence; 2) MB and LY-83583 blocked contraction but not the relaxation associated with SNP and NO; and 3) indomethacin blocked contractions but not the relaxation due to SNP, NO, and 8-BrcGMP. These results suggest that in the ELM, NO donors exert an inhibitory action that is largely cGMP independent and an excitatory action via a cGMP-dependent pathway involving endogenous eicosanoids of the cyclooxygenase pathway.
Saha
J K
JK
Center for Swallowing and Motility Disorders, Charles A. Dana Research Institute, Boston, Massachusetts.
Hirano
I
I
Goyal
R K
RK
D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D015777:Eicosanoids / Q000502:physiology*; D004947:Esophagus / Q000187:drug effects*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D009893:Opossums
D015777:Eicosanoids; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D007213:Indomethacin