title: Cholecystokinin receptor occupation and cholecystokinin-induced calcium mobilization in the early phase in rat pancreatic acini.
abstract: We examined receptor occupation, calcium mobilization and amylase release for cholecystokinin octapeptide (CCK-8) within a 3-min incubation period at 37 degrees C using dispersed acini from rat pancreas. Analysis of competitive binding inhibition data obtained after a 3-min incubation revealed the presence of only a single class of CCK receptors, while two classes of CCK receptor, i.e., high-affinity and low-affinity CCK receptors, were detected when binding reached a steady-state after a 60-min incubation. The IC50 of CCK receptors calculated from the 3-min binding data was 19.0 +/- 0.5 nM (mean +/- S.D.), close to the Kd of the low-affinity CCK receptors determined by equilibrium binding studies. Exposure of fura-2-loaded acini to 10-1000 pM CCK-8 caused an immediate and dose-dependent increase in [Ca2+]i followed by a gradual decrease in [Ca2+]i. The CCK-stimulated amylase release after 3 min of incubation was biphasic; amylase release increased over the dose range of 3-300 pM CCK-8, peaked at 300 pM CCK-8 and decreased with supramaximal concentrations of CCK-8. Our data suggest that occupation of the low-affinity, but not the high-affinity, CCK receptors is more directly associated with calcium mobilization and subsequent stimulation of amylase release in rat pancreatic acini.
authors.affiliation: GI Unit, Kyoto University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kusui
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Katsushima
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: C
authors.initials: C
authors.lastname: Shigeno
authors.forename: J
authors.initials: J
authors.lastname: Konishi
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D000681:Amylases; D002118:Calcium