Interaction between secretin and cholecystokinin‐octapeptide in the exocrine rat pancreas in vivo and in vitro

Abstract

SUMMARYThis study investigates the interaction between physiological doses of the synthetic gut hormones, cholecystokinin-octapeptide (CCK8) and secretin on pancreatic juice secretion in the anaesthetized rat and on amylase secretion and Ca2l and Mg2+ mobilization in isolated pancreatic segments and acinar cells. CCK8 (150 pmol kg-1 h-1) and secretin (100 pmol kg-1 h-1) evoked marked time course increases in pancreatic juice flow, total protein output and amylase secretion in the anaesthetized rat when administered separately compared to saline controls. Simultaneous intravenous infusion of CCK8 and secretin did not yield either an additive response or a potentiation but instead it caused a decrease in secretory responses. Administration of either polymyxin B (10-8 mol kg-1 h-1) or staurosporine (10-8 mol kg-1 h-1), two protein kinase C inhibitors, simultaneously with both CCK8 and secretin caused a further decrease in all secretory parameters. Superfusing pancreatic segments with either CCK8 (10-1 M) or secretin (10-1 M) elevated amylase output compared to the smaller response with a combination of CCK8 and secretin. Combining staurosporine (10-6 M) with CCK8 and secretin resulted in a further decrease in amylase output. CCK8 (10-1' M) evoked a large increase in radiolabelled Ca2+ influx into pancreatic segments and elevated cytosolic free Ca2+ concentration ([Ca2+]i) in acinar cells loaded with the fluorescent dye, Fura-2. Secretin (10-11 M) alone had no significant effect on Ca2+ mobilization but it markedly attenuated the increases in radiolabelled Ca2+ influx and [Ca2+]i elicited by CCK . In superfused pancreatic segments CCK8 (10-11 M) evoked a net efflux of Mg2+ whereas secretin (10-1' M) induced a net uptake of Mg2+. Combining secretin with CCK8 also resulted in a net uptake of Mg2+. The results indicate that both Ca2+ and Mg2+ mobilization may be associated with the interaction between CCK8 and secretin in the rat pancreas.

Interaction of Islet Hormones with Cholecystokinin Octapeptide‐Evoked Secretory Responses in the Isolated Pancreas of Normal and Diabetic Rats

“…However, the cellular mechanism(s) of the potentiation of fluid and enzyme secretion is still not clear. It is also possible that two or more intracellular mediators, including cellular Ca¥, cyclic AMP, protein kinase C and tyrosine kinase, are involved since two secretagogues acting via two or more different stimulus-secretion coupling pathways can potentiate one another (Schulz & Stolze, 1980;Jensen & Gardner, 1981;Williams, 1984;Singh, 1985b;Singh et al 1992). …”

“…For example the phorbol esters can potentiate the secretory actions of ACh and noradrenaline (NA) (Singh, 1985a;Francis & Singh, 1990) and attenuate enzyme secretion evoked by CCK-8 (Ansah et al 1986;Francis et al 1990a). Similarly, secretin can attenuate the secretagogue effect of CCK-8 and activation of intrinsic nerves in the rat pancreas (Singh et al 1992;Wisdom et al 1994).…”

“…The different secretagogues exert their stimulatory effect via four functionally distinct signal transduction pathways. Acetylcholine (ACh) and CCK-8 are known to stimulate cellular Ca¥ mobilization and protein kinase C whereas the effects of VIP, histamine, secretin or the catecholamines are associated with the metabolism of adenosine 3,5-cyclic monophosphate (cAMP) (Schulz & Stolze, 1980;Jensen & Gardner, 1981;Williams, 1984;Case, 1984;Singh et al 1992;Petersen, 1992). The growth factors exert their secretory effect by stimulating tyrosine kinase (Lajas et al 1996).…”

Composition of Gastric Juice and Bile in Rats at the Experimental Chronic Pancreatitis

“…табл.1). Отже, посилення секреції панкреатичного соку може бути пов'язано з ацидифікацією дванадцятипалої кишки, що в свою чергу викликає вивільнення секретину та холецистокініну -стимуляторів зовнішнь-осекреторної функції підшлункової залози [24]. На 68-му добу перебігу патології об'єм базальної панкреатичної секреції зменшився до 0,5 -1,0 мкл/год, тобто у тварин спостері-галася екзокринна недостатність підшлунко-вої залози, що відповідає клінічній картині хронічного панкреатиту.…”

Interaction between secretin and nerve‐mediated amylase secretion in the isolated exocrine rat pancreas

“…In several instances, workers have reported either a potentiation or an attenuation of secretory parameters between secretagogues (Jensen & Gardner, 1981;Singh, 1985;Ansah, Dho & Case, 1986;Willems, Van Nooij, Haenen & De Pont, 1987;Rosh, Schusdziarra, Wolf & Classen, 1989;Salido, Francis, Camello, Singh, Madrid & Pariente, 1990;Singh, Lennard, Salido, Wisdom, Render, Pozo & Pariente, 1992). However, no study has hitherto demonstrated any interaction between the gut hormones and activation of intrinsic secretomotor nerves in the regulation of exocrine pancreatic secretion.…”