Effect of sodium nitroprusside and 8-bromo cyclic GMP on nerve-mediated and acetylcholine-evoked secretory responses in the rat pancreas.
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. Electrical field stimulation (EFS; 10 Hz) and ACh (1 x 10(-5) M) caused large increases in amylase output from pancreatic segments. The response to ACh was blocked by atropine (1 x 10(-5) M) whereas the EFS-evoked response was markedly reduced but not abolished. In contrast, pretreatment with tetrodotoxin (1 x 10(-6) M) abolished the secretory effect of EFS. Either SNP (1 x 10(-3) M) or 8-Br-cyclic GMP (1 x 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. 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. 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. Nitric oxide may modulate the release of endogenous neural ACh in response to EFS in the rat pancreas.
Yago
Maria D
MD
Institute of Nutrition and Food Technology, Department of Physiology, University of Granada, 18071 Granada, Spain.
Tapia
Jose A
JA
Salido
Gines M
GM
Adeghate
Ernest
E
Juma
Lubna M O
LM
Martinez-Victoria
Emilio
E
Mañas
Mariano
M
Singh
Jaipaul
J
D000109:Acetylcholine / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020030:Nitric Oxide Donors; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D000681:Amylases; D006152:Cyclic GMP; D002794:Choline; D000109:Acetylcholine; D002118:Calcium