Phospholipase C Inhibitors Suppress Spontaneous Mechanical Activity of Guinea Pig Urinary Bladder Smooth Muscle

Abstract

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.

In vitro effects of the cyclooxygenase inhibitor indomethacin and of the phospholipase‐C inhibitor U‐73122 on carbachol‐induced contractions of porcine detrusor muscle

“…However, our results point to an inferior role of this pathway. Tanaka et al [19] showed that spontaneous mechanical activity of guinea pig urinary bladder smooth muscle is diminished by using U-73122, also used in our study, and additionally by another inhibitor of the phospholipase-C. Their results show a further role of phospholipase-C in myogenic contractions. Interestingly, Schneider et al [15] showed that U-73122 (1-10 lM) did not significantly affect the carbachol-stimulated bladder contraction of the rat urinary bladder.…”

“…Tanaka et al. [19] showed that spontaneous mechanical activity of guinea pig urinary bladder smooth muscle is diminished by using U‐73122, also used in our study, and additionally by another inhibitor of the phospholipase‐C. Their results show a further role of phospholipase‐C in myogenic contractions.…”

Vasorelaxation Effect and Mechanism of Action of Vascular Endothelial Growth Factor-165 in Isolated Perfused Human Skin Flaps

“…Specifically, the isolated perfused human skin flaps were preconstricted with 8 3 10 À7 M of NE. After 45 min of stabilization, the cumulative concentration-dependent relaxation induced by VEGF 165 (10 À15 -10 À10 M) was studied in the absence (control) and presence of 5 3 10 À6 M of the Src family tyrosine kinase inhibitor PP 2 [33], 5 3 10 À6 M of the phospholipase C (PLC) inhibitor NCDC (33), 5 3 10 À6 M of the inosital 1,4,5-triphosphate (IP 3 ) inhibitor 2-APB [34], 5 3 10 À6 M of the protein kinase C (PKC) inhibitor chelerythrine [35], or 5 3 10 À6 M of the intracellular Ca 2þ chelator BAPTA-AM [36].…”