Partial bladder outlet obstruction abolishes the receptor- and G protein-dependent increase in calcium sensitivity in rabbit bladder smooth muscle.
Partial bladder outlet obstruction (PBOO) alters the function of the whole bladder and produces specific alterations in the contractility of the bladder smooth muscle cell. The goal of this study was to test the hypothesis that PBOO affects smooth muscle contraction at the level of the receptor- and G protein-dependent increase in myofilament Ca2+ sensitivity. To address this question, we used alpha-toxin-permeabilized strips of bladder smooth muscle from control animals and animals subjected to 2 wk of PBOO. Increasing free [Ca2+] increased force in permeabilized strips from control animals; the addition of 10 microM carbachol and 10 microM GTP increased both the Ca2+ sensitivity of the contractions and the maximal levels of force attained. In contrast, although increases in [Ca2+] increased force in permeabilized strips from PBOO animals, the addition of carbachol and GTP had no additional effects. Myosin light chain phosphorylation levels increased with [Ca2+], and although they tended to be higher in strips from PBOO animals, they did not reach statistical significance. Assessment of G protein activity from both animal models suggests this is not a site responsible for the loss of carbachol and GTP enhancement of myofilament Ca2+ sensitivity. The addition of phorbol dibutyrate increased the Ca2+ sensitivity of force development in strips from both animal models, suggesting that an alteration in PKC signaling is not involved. Our results are consistent with the hypothesis that PBOO decreases receptor-mediated myofilament calcium sensitization and that the site of action is downstream from either the G proteins or PKC.
Stanton
Michaela C
MC
Dept. of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Delaney
Daniel
D
Zderic
Stephen A
SA
Moreland
Robert S
RS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D001743:Urinary Bladder / Q000378:metabolism*; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism*
D018679:Cholinergic Agonists; D018994:Myosin Light Chains; D006160:Guanosine Triphosphate; D002217:Carbachol; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium