Long-term stimulation of cAMP production in LLC-PK1 pig kidney epithelial cells by salmon calcitonin or a photoactivatable analogue of vasopressin.
A photoreactive analogue of vasopressin, [1-(3-mercapto)propionic acid, 8-(N6-4-azidophenylamidino)lysine]-vasopressin, was compared to salmon calcitonin and [8-arginine]-vasopressin with respect to stimulation of cAMP synthesis in the LLC-PK1 pig kidney epithelial cell line. Without photoactivation, the vasopressin analogue-elicited responses were identical to those induced by vasopressin, in that cAMP synthesis returned to the basal, unstimulated level about 4 h after hormonal treatment. In contrast, the levels of activation of cAMP-dependent protein kinase induced by salmon calcitonin returned to basal approx. 12 h after hormone addition. When activated by ultraviolet irradiation, the vasopressin analogue induced 'permanent' stimulation of adenylate cyclase, whereby cAMP production could be detected even 12.5 h after treatment. Both salmon calcitonin and the photoactivated vasopressin analogue inhibited growth of LLC-PK1 cells, in contrast to vasopressin or the nonactivated analogue. Growth inhibition appeared to be a consequence of the prolonged stimulation of adenylate cyclase. This conclusion was supported by the fact that a LLC-PK1 cell mutant in cAMP-dependent protein kinase was resistant to growth inhibition by salmon calcitonin and activated vasopressin analogue. The results imply that the cAMP-dependent protein kinase is the mediator of the hormone-stimulated growth inhibition.
Jans
D A
DA
Friedrich Miescher Institut, Basel, Switzerland.
Gajdas
E L
EL
Dierks-Ventling
C
C
Hemmings
B A
BA
Fahrenholz
F
F
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004848:Epithelium; D007668:Kidney; D007700:Kinetics; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism / Q000528:radiation effects; D013552:Swine; D014466:Ultraviolet Rays
C053818:vasopressin, 1-(3-mercapto)propionic acid-8-(N(6)-4-azidophenylamidino)lysine-; D001127:Arginine Vasopressin; D008236:Lypressin; D002116:Calcitonin; D000242:Cyclic AMP; D011494:Protein Kinases