title: Inositol triphosphate participates in an oestradiol nongenomic signalling pathway involved in accelerated oviductal transport in cycling rats.
abstract: 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.
authors.affiliation: Unidad de Reproducción y Desarrollo, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile. porihuel@bio.puc.cl
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Orihuela
authors.forename: Alexis
authors.initials: A
authors.lastname: Parada-Bustamante
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Zuñiga
authors.forename: Horacio B
authors.initials: HB
authors.lastname: Croxatto
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D004971:Estrus; D005187:Fallopian Tubes / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D007295:Inositol Phosphates / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects; D010066:Ovum Transport / Q000502:physiology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D010742:Phospholipid Ethers; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007295:Inositol Phosphates; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; C026659:edelfosine; D004958:Estradiol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D000225:Adenine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one