Effect of PGE1 on PGF2 alpha-induced luteolysis in nonbred ewes

Fifty-six ewes were used to study the effects of PGE1 or PGE2 plus PGF2 alpha given into the perivascular space of the ovarian vascular pedicle on luteal function of nonbred ewes. All ewes receiving PGF2 alpha had reduced levels of plasma progesterone and unoccupied receptors for LH at 24 hr after treatment regardless even if they received PGE1 or PGE2 concomitantly. Levels of plasma progesterone in ewes receiving only PGF2 apha were reduced further at 48 hour. Plasma progesterone and unoccupied receptors for LH of ewes receiving PGE2 + PGF2 alpha were maintained at 48 hr at levels seen at 24 hr after treatment, while progesterone in ewes receiving PGE1 + PGF2 alpha at 48 hr returned to levels seen in controls at 48 hr and unoccupied receptors for LH were three fold greater than controls.     

Adenosine facilitates the response to HCG, PGE1 or PGE2 and inhibits the response to PGF2 alpha by HCG-stimulated ovine luteal cells in vitro.

Dispersed ovine luteal cells collected on day 7 or 16 postestrus were incubated in vitro with hCG, PGE1 or PGE2 in the presence or absence of adenosine, dipyridamole (inhibitor of adenosine uptake) or PGF2 alpha in two separate experiments. Secretion of progesterone was increased by hCG, PGE1 or PGE2 when incubated with day 7 luteal cells (P less than or equal to 0.05) which was increased further when co-incubated with adenosine (P less than or equal to 0.05). PGF2 alpha alone or in the presence of hCG decreased (P less than or equal to 0.05) the secretion of progesterone by day 7 luteal cells, PGF2 alpha decreased post treatment cell viability with or without hCG (P less than or equal to 0.05) and adenosine reduced (P less than or equal to 0.05) the inhibitory effect of PGF2 alpha on hCG actions and luteal cell viability. Day 16 luteal cells were not functional based on jugular progesterone (P less than or equal to 0.05) and did not respond to hCG, PGE1, or PGE2 in the presence of adenosine or PGF2 alpha (P greater than or equal to 0.05). It is concluded that adenosine enhances the response of functional luteal cells to the luteotropins hCG, PGE1 or PGE2 and adenosine reduces the luteolytic response to PGF2 alpha by hCG-stimulated ovine luteal cells in vitro.     

Effects of prostaglandins E2 and F2alpha (PGE2; PGF2alpha), trilostane,mifepristone, palmitic acid (PA), indomethacin (INDO), ethamoxytriphetol (MER-25), PGE2 + PA,or PGF2alpha + PA on PGE2, PGF2alpha,and progesterone secretion by bovine corpora lutea of mid-pregnancy in vitro

The effects of PGE2, PGF2alpha, trilostane, RU-486, PA, INDO, MER-25, PGE2, or PGF2alpha + PA on secretion of progesterone, PGE2, or PGF2alpha by bovine corpora lutea (CL) of mid-pregnancy in vitro for 4 and 8 hr was examined. Secretion of PGE2 and PGF2alpha increased with time in culture (P < or = 0.05). PGE2 and PGE2 + PA increased (P < or = 0.05) secretion of progesterone at 4 and 8 h, progesterone secretion was increased (P < or = 0.05) at 4 h; but not at 8 h (P > or = 0.05) by trilostane, mifepristone, PGF2alpha and PGF2alpha + PA, and was decreased at 8 h by PGF2alpha and PGF2alpha + PA. Indomethacin decreased (P < or = 0.05) secretion of PGE2, PGF2alpha, and progesterone at 4 and 8 h. Trilostane, PA, PGF2alpha, RU-486 and PGF2alpha + PA increased (P < or = 0.05) PGE2 at 4 h only. Palmitic acid decreased (P < or = 0.05) PGF2alpha at 4 h, while trilostane, RU-486, or MER-25 did not affect (P < or = 0.05) PGE2 of PGF2alpha secretion. It is concluded that PGE2 of luteal tissue origin is the luteotropin at mid-pregnancy in cows. Also, it is suggested that PA may alter progesterone secretion by affecting the inter conversion of PGE2 and PGF2alpha.     

Activity of phospholipase C in ovine luteal tissue in response to PGF2 alpha, PGE2 and luteinizing hormone.

Four ewes were utilized to determine the effects of prostaglandin (PG) F2 alpha, PGE2 and luteinizing hormone (LH) on activity of phospholipase C (PLC) in ovine luteal tissue. Corpora lutea were collected on d 10 post-estrus and six slices from one corpus luteum from each ewe were pre-incubated with [3H]-inositol prior to incubation with one of 6 treatments. Treatments were 1) control, 2) PGF2 alpha (100 ng/ml), 3) PGE2 (10 ng/ml), 4) LH (10 ng/ml), 5) PGF2 alpha + PGE2 and 6) PGF2 alpha + LH. Phospholipase C was determined indirectly by measuring the accumulation of [3H]-inositol mono-, bis- and tris-phosphates (IP, IP2, IP3). Effects of PGF2 alpha (0 vs. PGF2 alpha) and luteotropic treatment (0 vs. PGE2 vs. LH) and their interactions were determined by analysis of variance. There was a significant main effect of PGF2 alpha (P less than 0.01) as concentrations of IP, IP2, IP3 and total [3H]-inositol phosphates were greater in tissue slices treated with PGF2 alpha, regardless of luteotropic treatment. Within groups receiving no PGF2 alpha (1,3,4), no effect of luteotropic treatment was observed. Within groups receiving PGF2 alpha (2,5,6), LH caused a significant (P less than .05) increase in the accumulation of total [3H]-inositol phosphates. Thus, PGF2 alpha can stimulate the activity of PLC in ovine luteal tissue and LH can potentiate this effect.     

Radioimmunoassay measurement of ACTH-facilitated PGE2 and PGF2alpha release from isolated cat adrenocortical cells.

Prostaglandin (PG) biosynthesis by trypsin-dispersed cat adrenocortical cells was studied by radioimmunoassay (RIA). Parallel assays of incubation media using PGF2alpha and PGF1alpha antisera established that PGF2alpha is the primary PGF released by feline cortical cells. Following the reduction of PGE to PGF with sodium borohydride (NaBH4) these same two antisera were also used to identify PGE2 as the primary PGE released. RIA using a PGE antiserum confirmed the presence of PGE in the incubation medium. Steroidogenic concentrations of ACTH (50-250muU) enhanced PGE and PGF release, and indomethacin suppressed the ACTH-facilitated release. These studies provide additional evidence for ACTH-induced PG synthesis by feline cortical cells, and support the hypothesis that PGs play some role in the steroidogenic action of ACTH.     

PGF2 alpha, PGE2, and sex steroids from the abdominal gland of the male crested newt Triturus carnifex (Laur.).

Prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), progesterone, androgens, and 17 beta-estradiol in vitro release by the abdominal gland of the crested newt, Triturus carnifex (Laur.), was studied during the prereproductive, reproductive and postreproductive periods. In addition, the in vitro effects of the PGF2 alpha and/or PGE2 on progesterone, androgens and estradiol release by the abdominal gland were evaluated. PGF2 alpha, PGE2 and progesterone release was higher during the reproductive period, and in the same period, PGE2 treatment induced a progesterone increase. PGF2 alpha induced an increase of abdominal gland estradiol release at the end of the reproductive period. These results seemed to confirm the pheromonal role assigned to progesterone, and suggested a PGE2 stimulatory role in inducing progesterone release, even if pheromonal activity of PGF2 alpha and PGE2 cannot be excluded. In addition, PGF2 alpha-dependent estradiol increase at the end of reproduction could be interpreted as a mechanism for interruption of the abdominal gland activity.     

PGE2 is a more potent vasodilator of the lamb ductus arteriosus than is either PGI2 or 6 keto PGF1alpha.

It has been shown in vitro that the lamb ductus arteriosus forms prostaglandins PGE2, PGF2alpha, 6 keto PGF1alpha (and its unstable precursor PGI2). In this study the relative potencies of these endogenous prostaglandins were investigated on isolated lamb ductus arteriosus preparations contracted by exposure to elevated PO2 and indomethacin. All the prostaglandins (except PGF2alpha) relaxed the vessel. This is consistent with the hypothesis that endogenous prostaglandins inhibit the tendency of the vessel to contract in response to oxygen. Only PGE2, however, relaxed the vessel at concentrations below 10(-8)M. PGI2 and 6 keto PGF1alpha had approximately 0.001 and 0.0001 times the activity of PGE2. Although PGE2 has been observed to be a minor product of prostaglandin production in the lamb ductus arteriosus, the tissue's marked sensitivity to PGE2 might make it the most significant prostaglandin in regulating the patency of the vessel.     

Isozyme specificity of rat liver glutathione S-transferases in the formation of PGF2 alpha and PGE2 from PGH2

When prostaglandin H2 (PGH2) was incubated with a mixture of glutathione S-transferases (GSTs) obtained from S-hexylglutathione affinity chromatography, as much as 40% of it was transformed into a prostanoid whose Rf value corresponded to that of the standard PGF2 alpha. The reaction product was identified as PGF2 alpha by cochromatography with a standard on TLC and HPLC. The stereochemistry of the hydroxyl groups on C-9 and C-11 of the cyclopentane ring was confirmed by mass-spectral analysis of the butylboronate derivative of the reaction product. Neither PGE2 nor PGD2 could substitute for PGH2 in the reaction mixture, indicating that the mechanism of formation of PGF2 alpha is a direct two-electron reduction of the endoperoxide moiety and not through a reduction of the keto group on PGE2 or PGD2. Individual GST isozymes exhibited distinct differences in their catalytic rates of formation of PGF2 alpha from PGH2. Among various GSTs, isozyme IV, a homodimer of Ya size subunit showed the highest activity with a Vmax value of approximately 6000 nmol.min-1.mg-1. In general, the isozymes containing Ya and Yc subunits exhibited relatively high activity toward PGH2, indicating that it is the non-selenium-dependent glutathione peroxidase activity associated with the GSTs that might be responsible for the reduction of PGH2 to PGF2 alpha. Interestingly, isozyme IV also exhibited the highest PGE2 forming activity with a Vmax value of approximately 3000 nmol.min-1.mg-1 followed by isozyme I, a homodimer of Yb subunit, which had a Vmax value of 420 nmol.min-1.mg-1. Based on these results, it appears that the GSTs play an important role in the biosynthesis of classical PGs. Therefore, it is conceivable that the tissue-specific formation of PGF2 alpha and PGE2 might, in part, be due to the relative distribution of these enzyme activities in a given tissue. Our results have not only confirmed the previously published reports (E. Christ-Hazelhof et al. (1976) Biochim. Biophys. Acta 450, 450-461), but also have characterized the specificity of GST isozymes in the formation of PGF2 alpha.     

PGE2 and PGF2alpha biosynthesis in stimulated and nonstimulated peritoneal preparations containing macrophages

The biosynthesis of PGE2 and PGF2alpha was measured in intact peritoneal exudate preparations obtained from C. parvum-treated and control C3H mice. Although both the control and stimulated preparations biosynthesized PGF2alpha and PGE2 from [1-14C] arachidonic acid, the stimulated preparations generated more of both prostaglandins than did nonstimulated preparations, probably as a result of increased synthesis within macrophages. Increased transformation of PGE2 into PGF2alpha by PGE2 9-ketoreductase was noted in stimulated preparations when compared to that in control cells. The data suggest that stimulated macrophages are capable of generating increased quantities of PGF2alpha and therefore might function as one source of this substance in resolving inflammatory reactions.     

Conversion of PGE2 to PGF2alpha by fetal sheep blood

In an attempt to explain the differences in the concentration of primary prostaglandins in the circulation of adult and fetal sheep, we have examined the ability of whole blood from adult and fetal sheep to reduce PGE2 to PGF2alpha in vitro. PGF2alpha was the principal radioactive product formed from 3H PGE2 by both adult and fetal blood. The enzyme initial reaction velocity was significantly higher (P = 0.02) per ml of fetal than adult blood. The optimum enzyme pH (7.0 - 7.5) was similar for both adult and fetal blood. The Km of the enzyme in fetal and adult blood were 3.59 x 10(-7) M and 5.02 x 10(-7) M respectively (P greater than 0.05). There was no detectable metabolism of PGF2alpha by either adult or fetal sheep blood. The results indicate that prostaglandin 9-ketoreductase is present in both adult and fetal sheep blood. Differences in the activity of this enzyme are unlikely to explain the higher concentrations of PGE reported in the plasma of fetal lambs.     

Influence of 15-keto-metabolites and 13,14-dihydro-15-keto-metabolites of PGE2 and PGF2 alpha as well as of 6-keto-PGF1 alpha as a metabolite of PGI2 on aconitine induced cardiac arrhythmia in rats

The 15-keto-metabolites of PGE2 and PGF2 alpha produced an antiarrhythmic effect on aconitine induced arrhythmias in rats. The ED50 values of these metabolites were approximately 2.0 micrograms/kg. The 13,14-dihydro-15-keto-metabolites of PGE2 and PGF2 alpha had no statistically significant antiarrhythmic effect. PGI2 (0.25-1.00 micrograms/kg) produced an antiarrhythmic effect between 15-54% (ED50 0.75 micrograms/kg), whereas 6-keto-PGF1 alpha, a metabolite of PGI2, showed no significant antiarrhythmic effect. The results suggest a participation of 15-keto-metabolites in the antiarrhythmic effects of PGE2 and PGF2 alpha.     

Role of progesterone in regulating uteroovarian venous concentrations of PGF2 alpha and PGE2 during the estrous cycle and early pregnancy in ewes

The role of progesterone in regulation of uteroovarian venous concentrations of prostaglandins F2 alpha(PGF2 alpha) and E2 (PGE2) during days 13 to 16 of the ovine estrous cycle or early pregnancy was examined. At estrus, ewes were either mated to a fertile ram or unmated. On day 12 postestrus, ewes were laparotomized and a catheter was inserted into a uteroovarian vein. Six mated and 7 unmated ewes received no further treatment. Fifteen mated and 13 unmated ewes were ovariectomized on day 12 and of these, 7 mated and 5 unmated ewes were given 10 mg progesterone sc and an intravaginal pessary containing 30 mg of progesterone. Uteroovarian venous samples were collected every 15 min for 3 h on days 13 to 16 postestrus. Mating resulted in higher mean daily concentrations of PGE2 in the uteroovarian vein than in unmated ewes. Ovariectomy prevented the rise in PGE2 with day in mated ewes but had no effect in unmated ewes. Progesterone treatment restored PGE2 in ovariectomized, mated ewes with intact embryos. Mating had no effect on mean daily concentrations of PGE2 alpha or the patterns of the natural logarithm (1n) of the variance of PGF2 alpha. Ovariectomy resulted in higher mean concentrations and 1n variances of PGF2 alpha on day 13 and lower mean concentrations and 1n variances of PGF2 alpha on days 15 and 16. Replacement with progesterone prevented these changes in patterns of mean concentrations and 1n variances of PGF2 alpha following ovariectomy. It is concluded that progesterone regulates the release of PGF2 alpha from the uterus, maintaining high concentrations while also preventing the occurrence of the final peaks of PGF2 alpha which are seen with falling concentrations of progesterone. This occurs in both pregnant and non-pregnant ewes. Progesterone is also needed to maintain increasing concentrations of PGE2 in mated ewes.     

Receptor binding in various tissues of PGE2, PGF2 alpha and sulprostone, a novel PGE2-derivative.

Sulprostone is a tissue-specific PGE2-derivative with high abortifacient activity in various species including man. The dissociation constant KD of the receptor binding of this compound was compared with PGE2 and PGF2 alpha in various tissue preparations of different species. A structure-binding relationship was developed from competition curves after a logit/log transformation. It is demonstrated that the relative affinities of Sulprostone, PGE2 and PGF2 alpha remain essentially constant in all the tissues investigated. It is concluded that the tissue-specificity of Sulprostone cannot be ascribed to structural differences of the receptor molecule.     

Biophysical studies on molecular mechanism of abortifacient action of prostaglandins. VI. Conformation energy calculation on PGE2, PGF2 alpha and 15-(s)-methyl PGF2 alpha

This paper reports the conformation energy (CE) calculations on PGE2, PGE2 alpha and 15-(s)-methyl PGE2 alpha on the basis of empirical potential energy functions for the simultaneous rotations around C7-C8 (psi), C12-C13 (theta) and C14-C15 (phi) bonds. The variation of the minimum conformation energy E for each isoenergy map in the psi theta plane with respect to phi gives two minima around 90 degrees and 240 degrees in PGE2, 60 degrees and 245 degrees in PGF2 alpha, and 60 degrees and 150 degrees in 15-(s)-methyl PGF2 alpha. The latter two forms also have a small dip at 270 degrees. The pattern of allowed low energy conformations of PGF2 alpha and 15-(s)-methyl PGF2 alpha is quite similar and is characterized by the existence of six low energy regions.     

Effects of the prostaglandins PGF2alpha and PGE2 on calcium signaling in rat hepatocyte doublets

Coordination of intercellular Ca2+ signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2alpha and PGE2, may modify these hepatocyte functions by inducing Ca2+ increase, but very little is known about the organization of the Ca2+ signals induced by these agonists. We studied Ca2+ signals induced by PGF2alpha and PGE2 in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca2+ oscillations, neither PGF2alpha nor PGE2 induced coordinated Ca2+ oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. Inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] assays and the increase in Ins(1,4,5)P3 receptor sensitivity to Ins(1,4,5)P3 observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of Ins(1,4,5)P3 formed by these prostaglandins. Furthermore, when PGE2 and PGF2alpha were added just before norepinephrine, they favored the coordination of Ca2+ signals induced by norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (>or=2 h) treatment with PGF2alpha, thereby preventing the coordination of Ca2+ oscillations induced by norepinephrine in these cells. Thus, depending on the time window, prostaglandins, specially PGF2alpha, may enhance or diminish the propagation of Ca2+ signals. They may therefore contribute to the fine tuning of Ca2+ wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism, or bile secretion, in both normal and pathogenic conditions.     

Proliferative effect of PGD2 on osteoblast-like cells; independent activation of pertussis toxin-sensitive GTP-binding protein from PGE2 or PGF2 alpha.

PGD2 stimulated DNA synthesis and decreased alkaline phosphatase activity dose-dependently between 10 nM and 10 microM in osteoblast-like MC3T3-E1 cells. PGD2 had little effect on cAMP production, but caused very rapid enhancement of phosphoinositide (PI) hydrolysis dose-dependently between 10 nM and 10 microM. The formation of inositol trisphosphate (IP3) induced by PGD2 reached the peak within 1 min and decreased thereafter, which is more rapid than that induced by PGE2 or PGF2 alpha and both PGE2 and PGF2 alpha affected PGD2-induced IP3 formation additively. Pertussis toxin (PTX) inhibited both PGD2-induced formation of inositol phosphates and DNA synthesis. The degree of these PTX (1 micrograms/ml)-induced inhibitions was similar. In addition, neomycin, a phospholipase C inhibitor, inhibited PGD2-induced DNA synthesis as well as the formation of IP3, and the patterns of both inhibitions were similar. In the cell membranes, PTX-catalyzed ADP-ribosylation of a 40-kDa protein was significantly attenuated by pretreatment of PGD2. Time course of the attenuation of PTX-catalyzed ADP-ribosylation by PGD2 was apparently different from that by PGE2 or PGF2 alpha. These results indicate that PGD2 activates PTX-sensitive GTP-binding protein independently from PGE2 or PGF2 alpha and stimulates PI hydrolysis resulting in proliferation of osteoblast-like cells.     

The effect of progesterone and human interferon alpha-2 on the release of PGF2 alpha and PGE from epithelial cells of human proliferative endometrium.

Progesterone and interferon-like trophoblastic proteins modulate prostaglandin (PG) synthesis from endometrium in early ovine and bovine pregnancy. Enriched epithelial cells were prepared from human endometrium removed in the proliferative phase of menstrual cycle (n = 8). Progesterone at a concentration of 1 microM suppressed PGE release from the cells during the first 24 hours in culture. After 48 hours in culture progesterone at a dose of 100 nM and 1 microM suppressed both the release of PGF2 alpha and PGE from the cells and this suppression was maintained for a further two days. Addition of exogenous 30 microM arachidonic acid (AA) abolished this effect of progesterone on both PGF2 alpha and PGE release. Interferon alpha-2 did not suppress the basal release of PGF2 alpha nor PGE. In the presence of progesterone, interferon alpha-2 attenuated the progesterone mediated suppression of PGF2 alpha but not PGE release from endometrial cells. These findings suggest that progesterone suppresses the basal release of PGs from human endometrium, but unlike the sheep, interferon alpha-2 does not exert this action on human endometrium.     

Inhibited skeletal muscle healing in cyclooxygenase-2 gene-deficient mice: the role of PGE2 and PGF2alpha.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat skeletal muscle injury. However, studies have shown that NSAIDs may be detrimental to the healing process. Mediated by prostaglandin F(2alpha) (PGF(2alpha)) and prostaglandin E(2) (PGE(2)), the cycloxygenase-2 (COX-2) pathway plays an important role in muscle healing. We hypothesize that the COX-2 pathway is important for the fusion of muscle cells and the regeneration of injured muscle. For the in vitro experiments, we isolated myogenic precursor cells from wild-type (Wt) and COX-2 gene-deficient (COX-2(-/-)) mice and examined the effect of PGE(2) and PGF(2alpha) on cell fusion. For the in vivo experiments, we created laceration injury on the tibialis anterior (TA) muscles of Wt and COX-2(-/-) mice. Five and 14 days after injury, we examined the TA muscles histologically and functionally. We found that the secondary fusion between nascent myotubes and myogenic precursor cells isolated from COX-2(-/-) mice was severely compromised compared with that of Wt controls but was restored by the addition of PGF(2alpha) or, to a lesser extent, PGE(2) to the culture. Histological and functional assessments of the TA muscles in COX-2(-/-) mice revealed decreased regeneration relative to that observed in the Wt mice. The findings reported here demonstrate that the COX-2 pathway plays an important role in muscle healing and that prostaglandins are key mediators of the COX-2 pathway. It suggests that the decision to use NSAIDs to treat muscle injuries warrants critical evaluation because NSAIDs might impair muscle healing by inhibiting the fusion of myogenic precursor cells.     

Actions of prostaglandins E1 and F2alpha on isolated intrapulmonary vascular smooth muscle.

The effects of PGE1 and PGF2alpha were studied on isolated strips of intrapulmonary arteries and veins from dog, sheep, swine and man. PGF2alpha contracted human arterial strips in a dose-dependent fashion, relaxed slightly sheep arteries and had no effect on dog arteries. Canine, sheep and human venous strips were contracted by PGF2alpha. PGE1 relaxed slightly both veins and arteries from dog and sheep. Human arteries usually contracted slightly and human veins usually relaxed slightly to PGE1. In a limited number of experiments, swine arteries and veins failed to respond to PGF2alpha or PGE1. All the vascular strips contracted well when exposed to NE. These results suggest that the responses of intrapulmonary vessels to PGF2alpha and PGE1 are species-dependent. PGF2alpha generally exhibits a contractile action, especially on veins. PGE1 usually relaxes intrapulmonary vessels. With regard to vessels from man, PGF2alpha is a powerful stimulant while PGE1 produces only small, variable effects.     

Effects of dopaminergic drugs on the concentrations of PGE2 and PGF2alpha in various brain regions

It has long been shown by Biggio and Guidotti that multisynaptic nigro-cerebellar pathway of dopaminergic origin can control cerebellar cyclic guanosinmonophosphate (cGMP) content, a good index of the activity of Purkinje cells. In this line, it has been reported that haloperidol and sulpiride, significantly decrease cerebellar cGMP content while opposite changes are observed with apomorphine. In an attempt to establish whether other cerebellar cGMP-related parameters may be influenced by dopamine drugs. Authors have investigated the effects of haloperidol, sulpiride and apomorphine on cerebellar PGE2 and PGF2alpha. Results obtained indicate that haloperidol and sulpiride significantly reduce cerebellar PGE2 and PGF2alpha content while opposite changes are induced by apomorphine. Similar results have been observed in substantia nigra but not in other brain regions, such as corpus striatum and medial basal hypothalamus. The possibility that the observed changes in cerebellar PG-content may result from the modulation of striatal dopamine receptors is discussed.