Effect of 3-isobutyl-1-methylxanthine and zaprinast on non-adrenergic non-cholinergic relaxation in the rat gastric fundus.

Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) have been proposed as inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitters in the rat gastric fundus. The smooth muscle relaxant actions of VIP and NO are medaited by cAMP and cGMP, respectively; therefore the effect of inhibitors of phosphodiesterases responsible for cyclic nucleotide breakdown on relaxation induced by VIP, NO and electrical field stimulation was investigated. The non-specific phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), the cGMP-specific phosphodiesterase inhibitor, zaprinast, the adenylate cyclase activator, forskolin, and the cyclic nucleotide analog, 8-bromo cGMP, produced concentration-dependent relaxation of rat gastric fundus strips precontracted by PGF2 alpha. IBMX potentiated isoprenaline-induced relaxation but not relaxation induced by sodium nitroprusside, VIP, NO or electrical field stimulation. Zaprinast potentiated the relaxation induced by sodium nitroprusside, while having no influence on relaxation due to any other stimulus. The combination of both phosphodiesterase inhibitors did not significantly affect the electrically induced relaxation. It is concluded that both cAMP and cGMP mediate relaxation in the rat gastric fundus. Further research is needed to investigate the role of the cyclic nucleotides during NANC relaxation of this tissue.