Phospholipase C inhibitors suppress spontaneous mechanical activity of guinea pig urinary bladder smooth muscle.
Urinary bladder smooth muscle (UBSM) exhibits spontaneous rhythmic contraction. This spontaneous mechanical activity is generated in the presence of neuronal blockade and thus is myogenic in origin. The spontaneous myogenic contraction of UBSM may be the fundamental determinant of the physiological functions of the urinary bladder to store and excrete urine. Although the mechanisms by which UBSM generates spontaneous contraction have not been completely ascertained, its induction has been suggested to be intimately associated with smooth muscle cell action potentials to enhance extracellular Ca(2+) influx through voltage-gated L-type Ca(2+) channels. However, the alteration of membrane electrical activity does not seem to be the exclusive trigger mechanism for the generation of the spontaneous contraction. In the present study, we show that spontaneous mechanical activity of guinea pig UBSM is substantially diminished by an inhibitor of phospholipase C (PLC), U-73122, but is not affected by its inactive form, U-73343. Significant attenuation of the mechanical activity can be also obtained with another PLC inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate. Our present findings suggest a significant role for the activation of PLC and subsequent inositol 1,4,5-trisphosphate-induced Ca(2+) release mechanism as an alternative triggering system for inducing spontaneous mechanical activity of UBSM. The present results support the idea that the action potential is not the sole pacemaker mechanism by which spontaneous contraction is induced in UBSM.
Tanaka
Yoshio
Y
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan. yotanaka@phar.toho-u.ac.jp
Okamoto
Takao
T
Imai
Toshiyasu
T
Horinouchi
Takahiro
T
Tanaka
Hikaru
H
Shigenobu
Koki
K
Koike
Katsuo
K
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology
D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; D010738:Type C Phospholipases