[Role of a guanine nucleotide regulatory protein in exocrine pancreatic secretion--effects of cholera toxin and pertussis toxin on cholecystokinin action].
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.
Matozaki
T
T
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Sakamoto
C
C
Nagao
M
M
Nishisaki
H
H
Konda
Y
Y
Baba
S
S
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D002766:Cholecystokinin / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D037342:Pertussis Toxin; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011949:Receptors, Cholecystokinin; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; D012969:Sodium Fluoride; D002766:Cholecystokinin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium