PT  - JOURNAL ARTICLE
AU  - M Barnette
AU  - T J Torphy
AU  - M Grous
AU  - C Fine
AU  - H S Ormsbee, 3rd
TI  - Cyclic GMP: a potential mediator of neurally- and drug-induced relaxation of opossum lower esophageal sphincter.
DP  - 1989 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 524--528
VI  - 249
IP  - 2
4099  - http://jpet.aspetjournals.org/content/249/2/524.short
4100  - http://jpet.aspetjournals.org/content/249/2/524.full
SO  - J Pharmacol Exp Ther1989 May 01; 249
AB  - Electrical field stimulation (EFS) of isolated strips of opossum lower esophageal sphincter (LES) produced a relaxation that was accompanied by an elevation of intracellular cyclic GMP content. In order to compare the time dependence of the EFS-induced relaxation with that of the elevation of cyclic GMP, the ability of EFS to produce relaxation and increase cyclic GMP was measured. The results of these experiments showed that cyclic GMP content increased before the onset of relaxation. Cumulative addition of atriopeptin II, an activator of particulate guanylate cyclase, produced a concentration-dependent relaxation of this tissue and increased cyclic GMP content. In other experiments, zaprinast, an inhibitor of a cyclic GMP selective-phosphodiesterase, produced a concentration-related relaxation of opossum LES and increased cyclic GMP content. However, pretreatment with zaprinast (3 microM) did not potentiate the EFS-induced relaxation or the increase in cyclic GMP content. At this concentration, however, zaprinast increased the basal content of cyclic GMP. Finally, 8-Br-cyclic GMP, a membrane-permeable analog of cyclic GMP, produced a concentration-dependent relaxation of isolated strips of opossum LES. In conclusion, these data extend the initial findings that an elevation in cyclic GMP content is associated with relaxation and suggest that cyclic GMP is a potential intracellular messenger of neurally- and drug-induced relaxation of opossum LES.