Islet activating protein inhibits kinin-stimulated inositol phosphate production, calcium mobilization, and prostaglandin E2 synthesis in renal papillary collecting tubule cells independent of cyclic AMP.
The effects of islet-activating protein (pertussis toxin) on bradykinin-mediated inositol trisphosphate labeling, prostaglandin E2 production, and calcium mobilization in rabbit renal papillary collecting tubule cells were assessed. Islet-activating protein induced time and concentration-dependent decreases in bradykinin-stimulated prostaglandin E2 production. Islet-activating protein induced increases in basal cyclic AMP levels but not in arginine vasopressin-stimulated cAMP. This effect could be inhibited by prior incubation with 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase. Although cAMP and cAMP analogues were able to inhibit both basal and bradykinin-stimulated prostaglandin E2 formation, the inhibitory effects of islet-activating protein on prostaglandin E2 formation and inositol trisphosphate labeling were observed in the presence of dideoxyadenosine. Moreover, islet-activating protein lowered both the basal and kinin-stimulated cytosolic calcium concentration as assessed by Quin 2 fluorescence. Finally, incubation of a membrane fraction of papillary cells with islet-activating protein resulted in the ADP-ribosylation of a 39/41-kDa doublet. These data support the role of a guanine nucleotide regulatory protein in bradykinin-mediated signal transduction in rabbit papillary collecting tubule cells.
Shayman
J A
JA
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
Morrissey
J J
JJ
Morrison
A R
AR
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000634:Aminoquinolines; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D015232:Dinoprostone; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007684:Kidney Tubules / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism; D007705:Kinins / Q000494:pharmacology*; D037342:Pertussis Toxin; D011458:Prostaglandins E / Q000096:biosynthesis*; D011817:Rabbits; D013403:Sugar Phosphates / Q000096:biosynthesis*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D000634:Aminoquinolines; D003839:Deoxyadenosines; D007295:Inositol Phosphates; D007705:Kinins; D011458:Prostaglandins E; D013403:Sugar Phosphates; D010566:Virulence Factors, Bordetella; D001127:Arginine Vasopressin; D000246:Adenosine Diphosphate Ribose; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D015232:Dinoprostone; C035739:Quin2; D002118:Calcium