Influence of bacterial toxins and forskolin upon vasopressin-induced inositol phosphate accumulation in WRK 1 cells.
The accumulation of inositol phosphates in WRK 1 cells, stimulated with a range of vasopressin concentrations, was diminished by prior exposure to cholera toxin or forskolin, whilst that observed in the presence of maximal concentrations of the hormone was enhanced in pertussis-toxin-treated cells. In the presence of [32P]NAD+, both cholera toxin and pertussis toxin provoked the labelling of peptides with approximate Mrs of 45,000 and 41,000 respectively in the membranes of WRK 1 cells. Exposure to cholera toxin or forskolin for 15-18 h enhanced cyclic AMP accumulation in these cells. The concentrations of these agents which provoked half-maximal cyclic AMP accumulation were similar to those required to diminish receptor-mediated inositol phosphate accumulation by 50%. In contrast, half-maximal ADP-ribosylation of the 45,000Mr peptide needed 100-fold greater concentrations of the toxin than were effective in provoking half-maximal inhibition of inositol phosphate accumulation. Cholera toxin or forskolin also reduced the maximal specific binding, to intact WRK 1 cells, of both [3H][Arg8]vasopressin and the V1a antagonist [3H][beta-mercapto-beta,beta-cyclopentamethylenepropionic acid,O-methyl-Tyr2, Arg8]vasopressin. The kinetics for the loss of this binding capacity following cholera-toxin treatment were very similar to those describing the diminution of vasopressin-stimulated inositol phosphate accumulation in the same cells.
Guillon
G
G
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Balestre
M N
MN
Lombard
C
C
Rassendren
F
F
Kirk
C J
CJ
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D037342:Pertussis Toxin; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects; D017483:Receptors, Vasopressin; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007295:Inositol Phosphates; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D005576:Colforsin; D000244:Adenosine Diphosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin