Opioid is the term used to designate a group of compounds that are opium-like in their properties. These drugs have
effects on perception of pain, consciousness, motor control, mood, and autonomic function, and can induce physical
dependence. Pharmacologic studies suggested that there are at least 3 major classes of opioid receptors, designated
delta, kappa, and mu. They differ in their affinity for various opioid ligands and in their cellular distribution.
Studies of the receptors in the mouse and rat show that they are structurally related and are members of the family of 7
transmembrane-spanning G protein-coupled receptors.
General function
Receptor
Comment
The involvement of protein kinases in signalling of opioid agonist FK 33-824 in porcine granulosa cells Kaminski T.
.
It is known that acute action of mu opioid receptor agonist, FK 33-824, results in an inhibition of oestradiol (E(2)) secretion by porcine granulosa cells from large follicles, but the opioid mode of action is unknown. In the present study, the involvement of two signal transduction pathways, phospholipase C/protein kinase C and adenylyl cyclase/protein kinase A, in mechanism of the opioid action was investigated. Treatment of pig granulosa cells with FK 33-824 at the dose 1nM suppressed E(2) secretion. Protein kinase C (PKC) inhibitors - staurosporine (1-100nM), d-sphingosine (10-500nM) and PKC(i) (100-2000nM) - both alone and in combination with FK 33-824 reduced E(2) release from the cells in relation to the control group. The inhibitory effect of the opioid on E(2) output was also observed in PKC-deficient granulosa cells. PKC activator, PMA (10 and 100nM) significantly attenuated the inhibitory effect of the opioid agonist. FK 33-824 also inhibited (3)[H]phorbol 12,13 dibutyrate ((3)[H]PDBu) specific binding by granulosa cells. Adenylyl cyclase (AC) engagement in opioid signal transduction was assayed after 2-h and 4-h incubations of granulosa cells. During 2-h incubation, FK 33-824 at the dose 1nM decreased cAMP secretion. Prolongation of the incubation up to 4h caused disappearance of the opioid action. The addition of protein kinase A (PKC) inhibitor, PKA(i) (100-2000nM), alone or together with FK 33-824, was followed by an inhibition of E(2) secretion. FK 33-824 with the highest dose of PKA(i) (2000nM) significantly inhibited E(2) secretion by the cells in comparison to these agents tested separately. The opioid added in combination with PKA activator, 8BrcAMP (1000muM), caused attenuation of stimulatory effect of 8BrcAMP. Collectively, these results suggest that acute action of mu opioid agonist on porcine granulosa cells leads to decrease of enzymatic activity of PKC and AC/PKA. It is not ruled out that other signal transduction pathways - not considered in this study - may also be engaged in the opioid mechanism of action in these cells.
Cellular localization
Plasma membrane
Comment
Ovarian function
Ovulation, Steroid metabolism
Comment
Gregoraszczuk EL, 1998 reported that beta-endorphin inhibits progesterone secretion by porcine granulosa cells
during follicle development.
Faletti A, et al reported that beta-endorphin inhibits prostaglandin synthesis in rat ovaries
and blocks induced ovulation
in ovaries isolated from pregnant mare's serum gonadotropin/human
chorionic gonadotropin(PMSG/hCG)-primed immature rats. An intrabursal
injection of the opioid (0.084 microgram) was given 4 hours after hCG and the
number of oocytes within the oviducts on the following morning was reduced (P <
0.05). The same effect was also attained with an intraperitoneal (IP) injection (0.5
microgram).
Kato T et al reported the effect of beta-endorphin on cAMP and progesterone
accumulation in rat luteal cells.
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
Comment
Slomczynska M, et al 1997 reported that the kappa-opioid receptor is present in porcine ovaries and localized to granulosa cells.
They
showed that the level of alpha-neoendorphin which derives from prodynorphin
changes in folliculogenesis. The lowest level was observed in the small follicles,
increased in the medium, and reached the highest level in the preovulatory
follicles. The presence of the kappa-opioid receptor in granulosa cells, obtained
from follicles of varying sizes was demonstrated. The monoclonal
anti-kappa-opioid receptor antibody was used to reveal the expression of
kappa-opioid receptor.
Expression and localization of opioid receptors during the maturation of human oocytes. Agirregoitia E et al. The endogenous opioid system has been characterized in some female reproductive organs, but little is known about the expression of these receptors in human oocytes. This study investigated the presence and differential distribution of the opioid receptors during the maturation of human oocytes. A total of 821 human oocytes from an intracytoplasmic sperm injection (ICSI) programme were studied including 213 at germinal-vesicle (GV) stage and 164 at metaphase-I (MI) stage and 444 failed fertilization metaphase-II (MII) oocytes. Additionally 31 MII oocytes corresponding to cases where ICSI was not attempted and 50 failed fertilization MII oocytes from the IVF programme were included. Western blot analysis revealed the presence of the delta (OPRD1), kappa (OPRK1) and mu (OPRM1) opioid receptors in human oocytes. The OPRK1 and OPRM1 immunostaining patterns changed during the maturation of the oocyte, while the OPRD1 pattern was the same throughout. In particular, OPRD1 were detected in peripheral tissue from the GV to the MII stage. OPRK1 were found peripherally at the GV stage, more internally at MI and homogeneously at MII. Finally, OPRM1 were located peripherally at the GV stage and homogeneously in MI and MII oocytes. Opioids may have a role in oocyte maturation, acting via receptors. The opioid system has been well characterized in the central nervous system, but it is now known that opioids also act in reproductive organs. However, little is known about the presence and function of this system in human oocytes and its role in their maturation. In this study, we investigated the presence and differential distribution of three (delta, kappa and mu) opioid receptors (proteins which bind the opioids) during the maturation of human oocytes. A total of 821 human oocytes (from 253 patients) not suitable for intracytoplasmic sperm injection (ICSI) or which did not develop into an embryo after ICSI were studied. Thus, we have verified the presence of the delta, kappa and mu opioid receptors in human oocytes. The kappa and mu localization changed during the maturation of the oocyte, while the Delta localization was the same throughout. In particular, the delta receptor was detected in the periphery of the oocyte. On the other hand, the kappa receptor was found peripherally at the beginning, more internally during maturation and homogeneously at the end of maturation. Finally, the Mu receptor was located peripherally at the beginning of maturation and homogeneously in the rest of the maturation stages. This finding suggests a possible role for opioids, acting via receptors, in the maturation of the oocyte.