Isoproterenol induces mitogenesis in MCT and LLC-PK1 tubular cells.
This study assessed the effects of exogenous isoproterenol on the proliferation of the proximal tubular cell lines MCT and LLC-PK1. Both cell lines express beta-adrenergic receptors as demonstrated by Scatchard analysis of binding data, receptor-cross linking studies, and mRNA expression for beta 2-adrenergic receptors. Isoproterenol (10(-7) M) for 15 min stimulated the formation of intracellular cAMP in MCT cells (controls, 8.0 +/- 0.7; isoproterenol, 12.6 +/- 0.89 fmol of cAMP/microgram of protein; P < 0.01). This effect was blocked by the beta-receptor antagonist propranolol (10(-6) M). Isoproterenol, in a dose-dependent manner, also induced proliferation in MCT and LLC-PK1 cells, as measured by [3H]thymidine incorporation and direct cell counts. Time-course experiments demonstrated maximal mitogenesis 48 h after a single dose of 10(-7) M isoproterenol. This mitogenic effect was mimicked by a stable cAMP analog or cholera toxin, but not by a cGMP analog, indicating that the isoproterenol-mediated growth effects are likely caused by cAMP. These results provide evidence that isoproterenol is a mitogenic growth factor for cultured proximal tubular cells. These findings may be important in the growth mechanisms involved in the proliferative remodeling of injured tubules after acute renal failure.
Wolf
G
G
Department of Medicine, University of Hamburg, Germany.
Neilson
E G
EG
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000187:drug effects; D013552:Swine
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol