title: Long-term stimulation of cAMP production in LLC-PK1 pig kidney epithelial cells by salmon calcitonin or a photoactivatable analogue of vasopressin.
abstract: 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.
authors.affiliation: Friedrich Miescher Institut, Basel, Switzerland.
authors.forename: D A
authors.initials: DA
authors.lastname: Jans
authors.forename: E L
authors.initials: EL
authors.lastname: Gajdas
authors.forename: C
authors.initials: C
authors.lastname: Dierks-Ventling
authors.forename: B A
authors.initials: BA
authors.lastname: Hemmings
authors.forename: F
authors.initials: F
authors.lastname: Fahrenholz
mesh_terms: 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
chemical_list: 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