MODULATION OF PHOSPHOLIPASE-C PATHWAY AND LEVEL OF G(Q)ALPHA G(11)ALPHA IN RAT MYOMETRIUM DURING GESTATION/

The regulation of the receptor-a protein-phospholipase C (PLC) cascade was investigated in rat myometrium at midgestation (day 12) and at te rm (clay 21) comparatively to the estrogen-treated tissue (day 0). Car bachol-mediated generation of [H-3]inositol phosphates was insensitive to pertussis toxin and was enhanced at days 12 and 21 two- and threef old, respectively, with no alteration of muscarinic sites (M(3) sub-ty pe). A similar increase could be detected in the production of inosito l 1,4,5-trisphosphate, indicating the stimulation of a PLC degrading p hosphatidylinositol 4,5-bisphosphate. AIF(4)(-) also enhanced PLC acti vation during gestation, suggesting pregnancy-related regulations that bypass receptor activation. Immunoreactive G proteins, G(q) alpha and G(11)alpha, and PLC-beta(3) were detected in all myometrial preparati ons. The amount of PLC-beta(3) was similar in day 0 and day 21 myometr ium, although decreasing by 75% at midgestation. Of significance was t he increased amount of G(q) alpha in day 12 and day 21 myometrium (3- and 2-fold, respectively) which coincided with the enhanced phosphoino sitide breakdown. The upregulation of G(q) alpha may contribute to the enhanced PLC activity during pregnancy and at term.