e initial steps in the steroidogenic process. specifically, these cells convert acetate or cholesterol to androgens, which are secreted into the intra follicular medium and taken up by granulosa cells to serve as substrate for estro gen synthesis. In addition, theca cells could be an impor tant signal integrator and regulator of aspects of follicular Volasertib aml growth, because it represents the last follicular layer in contact with blood flow and receives chemical informa tion from the peripheral nervous system. Several studies in recent years indicate that the puriner gic signaling system is functionally e pressed in the ovary of several species and represents another regulatory element in ovarian physiology. however, the physiological role of ATP in this conte t and its membrane receptors is unknown.
ATP is an important neurotransmitter in the peripheral nervous system, and nerve terminals from this system are potential sources for ATP release in the ovary. For e ample, the ovary is innervated by sympathetic termi nals through the superior ovarian nerve and ovarian ple us. It has been shown in other tissues that ATP is co released with noradrenaline by sympathetic termi nals and that it participates in several physiological events such as the induction and regulation of smooth muscle contraction and the modulation of cardiac muscle e citation. In addition, several cell types are able to release ATP in a basal manner and or in response to different stimuli, such as mechanical stimulation, changes in pH, or hypotonic stress.
As a cellular messenger, ATP e erts its action through membrane receptors named P2, which are grouped into two subfamilies P2 receptors that are cationic channels, and P2Y receptors that belong to the G protein coupled receptor super family. In mammals, 8 subtypes of P2Y receptors have been described 1, 2, 4, 6, and 11 14. Subtypes P2Y1, 2, 4, 6, and 11 are mainly coupled to Gq 11 proteins, and they activate phospholipase C and consequently diacylglycerol and phosphoinositide Ca2 turnover. subtypes 12 14, on the other hand, are coupled to Gi 0 proteins that signal primarily by inhibiting adeny lyl cyclase. P2Y2, P2Y4, and P2Y6 form a subgroup of receptors sensitive to uridine nucleotides, P2Y2 and P2Y4 show selectivity for nucleoside triphosphates, while P2Y6 prefers mainly nucleoside diphosphates, specifically UDP.
Uridine P2Y activated receptors are involved Carfilzomib in a broad variety of physiological processes such as cell pro liferation, smooth muscle contraction, transmitter selleckchem U0126 release, and others. In the ovary, e pression of UTP sensitive P2Y receptors has been described in gran ulosa luteal cells, in the cumulus cell oocyte com ple , and in enopus ovarian follicles. Recently, it was demonstrated that functional P2 7 receptors are e pressed in mammalian TIC and can induce apoptotic cell death. In the same study, it was also observed that the application of UTP evoked intrac ellular i changes, suggesting that multiple P2 recep tor subtypes ar