title: Regulation of fluid secretion and intracellular messengers in isolated rat pancreatic ducts by acetylcholine.
abstract: 1. We have studied the effects of acetylcholine (ACh) on fluid secretion and intracellular messengers in interlobular ducts isolated from the rat pancreas and maintained in short-term tissue culture. 2. Ductal fluid secretion was measured using micropuncture techniques. Intracellular free calcium ([Ca2+]i) and cyclic AMP concentrations were measured in single ducts using fura-2 microspectrofluorimetry and radioimmunoassay techniques respectively. Changes in the levels of these intracellular messengers were correlated with fluid secretion. 3. ACh stimulated ductal fluid secretion. The dose required for a half-maximal response was about 0.4 microM and maximal secretion was achieved with 10 microM ACh. These effects of ACh were blocked by atropine and by removal of extracellular Ca2+. 4. ACh was about four orders of magnitude less potent as an activator of ductal fluid transport than the hormone secretin; however, the maximal rates of fluid secretion evoked by these two agonists were similar. 5. ACh caused a dose-dependent rise in duct cell [Ca2+]i, but had no effect on cyclic AMP. In contrast, secretin increased duct cell cyclic AMP, but had no effect on [Ca2+]i. 6. The [Ca2+]i response evoked by ACh resulted from both mobilization of intracellular Ca2+ stores and influx of Ca2+ from the extracellular space. 7. The Ca2+ ionophore, ionomycin, mimicked the effect of ACh on ductal [Ca2+]i and fluid secretion. 8. We conclude that ACh stimulates fluid secretion from rat pancreatic duct cells by activating a 'Ca2+ pathway' which is distinct from the well documented 'cyclic AMP pathway' utilized by secretin.
authors.affiliation: Department of Physiological Sciences, University Medical School, Manchester.
authors.forename: N
authors.initials: N
authors.lastname: Ashton
authors.forename: R L
authors.initials: RL
authors.lastname: Evans
authors.forename: A C
authors.initials: AC
authors.lastname: Elliott
authors.forename: R
authors.initials: R
authors.lastname: Green
authors.forename: B E
authors.initials: BE
authors.lastname: Argent
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D010183:Pancreatic Ducts / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D012633:Secretin / Q000494:pharmacology
chemical_list: D012633:Secretin; D015759:Ionomycin; D000242:Cyclic AMP; D000109:Acetylcholine; D002118:Calcium