INHIBITORY EFFECT OF ZINC PROTOPORPHYRIN-IX ON LOWER ESOPHAGEAL SPHINCTER SMOOTH-MUSCLE RELAXATION BY VASOACTIVE INTESTINAL POLYPEPTIDE ANDOTHER RECEPTOR AGONISTS

This study was performed in the opossum lower esophageal sphincter (LE S) smooth muscle strips to determine the action of the heme oxygenase inhibitor zinc protoporphyrin IX (ZnPP IX) on the relaxant effect of v asoactive intestinal polypeptide and isoproterenol, which are known to stimulate adenylate cyclase (AC) via G protein coupling, and of the d irect activator of AC catalytic subunit forskolin. To investigate the cGMP pathway, we examined the effect of atrial natriuretic factor know n to activate the receptor linked to the particulate guanylate cyclase via G protein coupling and that of sodium nitroprusside [nitric oxide (NO) donor], authentic NO and carbon monoxide, which stimulate the in tracellular soluble fraction of GC. The smooth muscle relaxation cause d by nonadrenergic noncholinergic (NANC) nerve stimulation also was in vestigated. ZnPP IX caused concentration-dependent attenuation of the relaxant effect of vasoactive intestinal polypeptide, isoproterenol an d atrial natriuretic factor without any effect on that of forskolin, s odium nitroprusside, NO and CO. Interestingly, ZnPP IX had no signific ant effect on the LES relaxation caused by NANC nerve stimulation and the smooth muscle contraction by bethanechol. From these results, we c onclude that ZnPP IX attenuates the LES smooth muscle relaxation cause d by the stimulation of G protein-coupled receptors to particulate AC and guanylate cyclase. The lack of effect of ZnPP IX on the NANC nerve -mediated LES relaxation suggests either lack of a role of heme oxygen ase pathway in the response or an up-regulation of NOS leading to norm al LES relaxation.