Abstract
In the guinea pig gastric antrum, the effects of sodium nitroprusside (SNP), an NO donor, on pacemaker potentials were investigated in the presence of nifedipine. The pacemaker potentials consisted of primary and plateau components; SNP (> 1 microM) increased the frequency of occurrence of these pacemaker potentials, while inhibiting the plateau component. 1H-[1,2,4]-Oxadiazole [4,3-a] quinoxalin-1-one, an inhibitor of guanylate cyclase, had no effect on the excitatory actions of SNP on the frequency of pacemaker potentials. Other types of NO donor, (+/-)-S-nitroso-N-acetylpenicillamine, 3-morpholino-sydnonimine and 8-bromoguanosine 3'5'-cyclic monophosphate had no excitatory effect on pacemaker activity. Forskolin, an activator of adenylate cyclase, or 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid, an inhibitor of the Ca(2+)-activated Cl(-) channel, strongly attenuated the generation of pacemaker potentials, and SNP added in the presence of these chemicals restored the generation of pacemaker potentials. The pacemaker potentials evoked by SNP were abolished in low-Ca(2+) solution or by membrane depolarization with high-K(+) solution. The SNP-induced generation of pacemaker potentials was not prevented by cyclopiazonic acid, an inhibitor of internal Ca(2+)-ATPase, but was limited to a transient burst by iodoacetic acid, an inhibitor of glycolysis, carbonyl cyanide m-chlorophenyl-hydrazone, a mitochondrial protonophore, or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, an intracellular Ca(2+) chelator. These results suggest that the SNP-induced increase in the frequency of pacemaker potentials is related to the elevated intracellular Ca(2+) concentrations due to release from mitochondria, and these actions may be independent of the activation of guanylate cyclase.
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