Role of a guanine nucleotide regulatory protein in exocrine pancreatic secretion--effects of cholera toxin and pertussis toxin on cholecystokinin action

• Published in: Nippon Naibunpi Gakkai zasshi Vol. 65; no. 8; p. 743
• Main Authors: Matozaki, T, Sakamoto, C, Nagao, M, Nishisaki, H, Konda, Y, Baba, S
• Format: Journal Article
• Language: Japanese
• Published: Japan 20.08.1989
• Subjects: Adenosine Diphosphate - metabolism; Animals; Calcium - metabolism; Catalysis; Cholecystokinin - pharmacology; Cholera Toxin - pharmacology; GTP-Binding Proteins - metabolism; GTP-Binding Proteins - physiology; Hydrolysis; In Vitro Techniques; Inositol Phosphates - metabolism; Male; Pancreas - metabolism; Pertussis Toxin; Phosphatidylinositol Phosphates; Phosphatidylinositols - metabolism; Rats; Receptors, Cholecystokinin - metabolism; Sodium Fluoride - pharmacology; Virulence Factors, Bordetella - pharmacology
• ISSN: 0029-0661
• DOI: 10.1507/endocrine1927.65.8_743

We have recently shown that F- can mimic the actions of cholecystokinin (CCK) on amylase release, Ca2+ mobilization and inositol phosphate generation in pancreatic acinar cells. We have concluded, therefore, that pancreatic CCK receptors may be coupled to the activation of polyphosphoinositide hydrolysis by a guanine nucleotide regulatory protein (N protein), which seems to be sensitive to F-. In the present study, in order to further characterize this N protein coupled to pancreatic CCK receptors, we have examined the effects of bacterial toxins, pertussis toxin (PT) and cholera toxin (CT) on both CCK- and NaF-induced cellular responses in isolated rat pancreatic acini. Neither PT or CT pretreatment of acini affected both CCK- and NaF-stimulated increases in intracellular Ca2+ concentration monitored by quin2. Furthermore, pretreatments of acini with PT and CT didn't alter the effects of CCK on inositol phosphate generation in acini. Similarly, NaF-induced inositol phosphate generation was not changed by these toxin treatments. However, pretreatment procedures employed in this study were considered to catalyze complete ADP-ribosylation of alpha-subunit of the stimulatory (Ns) and inhibitory (Ni) N protein. These results, therefore, strongly suggest that a N protein coupling pancreatic CCK receptors to the breakdown of polyphosphoinositide may be distinct from Ns or Ni like protein.