Effects of Bordetella pertussis toxin on catecholamine inhibition of insulin release from intact and electrically permeabilized rat islets.
Noradrenaline- and clonidine-induced inhibition of insulin release from intact and electrically permeabilized rat islets was markedly relieved by prior exposure to 100 ng of Bordetella pertussis toxin/ml. The reversal of catecholamine inhibition of insulin secretion by this toxin was not associated with a decrease in specific binding of the alpha 2-adrenergic ligand [3H]yohimbine, and could not be fully explained by an increase in intracellular cyclic AMP. Exposure of intact islets to 1 microgram of pertussis toxin/ml for 2 h, followed by electrical permeabilization and incubation with 5 microCi of [alpha-32P]NAD+, resulted in the ADP-ribosylation in situ of a protein of molecular mass approx. 41 kDa. These results suggest that pertussis toxin alleviates catecholamine inhibition of beta-cell secretory responses by ADP-ribosylating at least one protein of molecular mass 41 kDa. In analogous systems the 41 kDa substrate of pertussis toxin has been shown to be the alpha subunit of Gi, but catecholamine-activated G proteins linked to effector systems other than adenylate cyclase might also be modified by this toxin in pancreatic beta-cells.
Persaud
S J
SJ
Department of Physiology, King's College London, University of London,U.K.
Jones
P M
PM
Howell
S L
SL
D037361:Adenylate Cyclase Toxin; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003000:Clonidine / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D015016:Yohimbine / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D007328:Insulin; D010566:Virulence Factors, Bordetella; D015016:Yohimbine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine