Effect of sodium nitroprusside and 8-bromo cyclic GMP on nerve-mediated and acetylcholine-evoked secretory responses in the rat pancreas

1. The effects of sodium nitroprusside (SNP) and 8-bromo-guanosine 3′5′ cyclic monophosphate (8-Br-cyclic GMP) on nerve-mediated and acetylcholine (ACh)-evoked amylase secretion, tritiated choline ([³H]-choline) release and on intracellular free calcium concentration ([Ca²⁺]_i) in the isolated rat pancreas were investigated. 2. Electrical field stimulation (EFS; 10 Hz) and ACh (1 × 10^-5 M) caused large increases in amylase output from pancreatic segments. The response to ACh was blocked by atropine (1 × 10^-5 M) whereas the EFS-evoked response was markedly reduced but not abolished. In contrast, pretreatment with tetrodotoxin (1 × 10^-6 M) abolished the secretory effect of EFS. 3. Either SNP (1 × 10^-3 M) or 8-Br-cyclic GMP (1 × 10^-4 M) inhibited amylase secretion compared to basal. Combining either SNP or 8-Br-cyclic GMP with EFS resulted in a marked decrease in amylase output compared to EFS alone. In contrast, either SNP or 8-Br-cyclic GMP had no significant effect on the amylase response to ACh. When extracellular Ca²⁺ concentration ([Ca²⁺]_o) was elevated from 2.56 mM to 5.12 mM, SNP failed to inhibit the response to EFS. 4. EFS stimulated the release of ³H from pancreatic segments preloaded with [³H]-choline. Either SNP or 8-Br-cyclic GMP had no effect on basal ³H release but significantly reduced the EFS-evoked response. 5. In fura-2 loaded acinar cells, SNP elicited a small decrease in [Ca²⁺]_i compared to basal and had no effect on the ACh-induced [Ca²⁺]_i peak response. 6. Nitric oxide may modulate the release of endogenous neural ACh in response to EFS in the rat pancreas.