| 16522737 |
Orihuela PA, Parada-Bustamante A, Zuniga LM, Croxatto HB: Inositol triphosphate participates in an oestradiol nongenomic signalling pathway involved in accelerated oviductal transport in cycling rats. J Endocrinol. 2006 Mar;188(3):579-88.
Oestradiol (E (2)) accelerates oviductal transport of oocytes in cycling rats through a nongenomic pathway that involves the cAMP-PKA signalling cascade. Here we examined the role of the inositol triphosphate (IP3) and mitogen-activated protein kinase (MAPK) signalling cascades in this nongenomic pathway. Oestrous rats were injected with E (2) s.c. and intrabursally (i.b) with the selective inhibitors of phospholipase C (PLC) ET-18-OCH (3) or MAPK PD98059. The number of eggs in the oviduct assessed 24 h later showed that ET-18-OCH (3) blocked E (2)-induced egg transport acceleration, whereas PD98059 had no effect. Other oestrous rats were treated with E (2) s.c. and 1, 3 or 6 h later oviducts were excised and the levels of IP3 and phosphorylated MAPK p44/42 (activated) were determined by radioreceptor assay and western blot, respectively. Oestradiol administration increased IP3 level at 1 and 6 h after treatment, whereas activated MAPK p44/42 level was unchanged. Finally, we explored whether cAMP-PKA and PLC-IP3 signalling cascades are coupled. Inhibition of adenylyl cyclase by i.b. injection of SQ 22536 blocked the increase of IP3 levels induced by E (2), while inhibition of PLC by ET-18-OCH (3) had no effect on E (2)-induced PKA activity. Furthermore, activation of adenylyl cyclase by Forskolin increased oviductal IP3 levels. Thus, activation of PLC-IP3 by E (2) requires previous stimulation of cAMP-PKA. We conclude that the nongenomic pathway utilised by E (2) to accelerate oviductal transport of oocytes in cycling rats involves successive activation of the cAMP-PKA and PLC-IP3 signalling cascades and does not require activation of MAPK. These findings clearly illustrate a non-genomic pathway triggered by E (2) that regulates a complex physiologic process accomplished by an entire organ. |
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