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B M Cox

Publications and source records attributed to B M Cox.

At least 55 records · Page 3Linked to original sources
PubMed1990

Daily cocaine treatment produces a persistent reduction of [3H]dopamine uptake in vitro in rat nucleus accumbens but not in striatum.

Daily administration of cocaine (15 mg/kg i.p. x 3 days) led to a decrease in the total amount of 15 nM [3H]dopamine uptake in rat nucleus accumbens with no change in uptake in the striatum when tested 24 h after the last injection. There was an increase in the Km for dopamine uptake in the nucleus accumbens of cocaine-treated rats, with no change in the Vmax. Furthermore, cocaine was a more potent inhibitor of [3H]dopamine uptake in vitro in the nucleus accumbens of rats treated with cocaine than in those which had received saline.

Animals↗
PubMed1990

Comparison of the effects of cocaine and other inhibitors of dopamine uptake in rat striatum, nucleus accumbens, olfactory tubercle, and medial prefrontal cortex.

It is thought that inhibition of dopamine reuptake into neurons may play a major role in the mechanisms by which cocaine produces its reinforcing effects. The striatum, while rich in dopamine terminals, is not implicated in drug reinforcement, whereas the mesolimbic dopamine pathway appears to play a primary role. It is therefore possible that the properties and drug sensitivities of the dopamine uptake systems in the nigrostriatal, mesolimbic, and mesocortical tracts differ. The effects of cocaine, GBR 12909, amfonelic acid, and methylphenidate on dopamine uptake in the striatum, nucleus accumbens, olfactory tubercle, and medial prefrontal cortex were examined. Over 80% of the dopamine uptake in each of the 4 regions was sodium-dependent and exhibited Km values of approximately 100 nM. Cocaine, GBR 12909, amfonelic acid, and methylphenidate each biphasically inhibited uptake in the striatum, nucleus accumbens and olfactory tubercle with GBR 12909 and amfonelic acid being approximately 50-fold more potent than cocaine or methylphenidate. In the medial prefrontal cortex, cocaine and GBR 12909 could inhibit only about 40% of the [3H]dopamine uptake. There are similarities in the properties and drug sensitivities of the dopamine uptake systems in brain areas which are implicated in drug reinforcement and those which are not.

Animals↗
PubMed1990

Characterization of binding of [3H]GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine) to membranes and to solubilized membrane extracts from terminal field regions of mesolimbic, mesocortical and nigrostriatal dopamine pathways.

The binding characteristics of [3H]GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine), a selective dopmaine uptake inhibitor, were examined in intact membrane preparations and solubilized extracts of terminal field regions of dopamine pathways in the brain of the rats. There were many similarities in the properties of binding sites for [3H]GBR 12935 in the striatum, nucleus accumbens and olfactory tubercle. The binding of [3H]GBR 12935 was saturable and the affinity constants were not significantly different between regions of the brain. The binding of [3H]GBR 12935 was inhibited by amfonelic acid, GBR 12909, mazindol, methylphenidate and cocaine, with comparable affinities in each region of the brain and with the same order of potency in both preparations. Furthermore, the rank order of potencies for inhibiting the binding of [3H]GBR 12935 was the same as for inhibiting the uptake of [3H]dopamine in these regions of the brain. There did appear to be some degree of heterogeneity of binding sites for [3H]GBR 12935 in each of these regions of the brain, as both amfonelic acid and mazindol were best fitted by two-site models. Whether this apparent heterogeneity was due to the existence of two distinct binding sites or to two components of a single site is unclear. It did not, however, appear to be due to binding to uptake sites for norepinephrine or serotonin, as neither nisoxetine nor fluoxetine, selective inhibitors of the uptake of norepinephrine and serotonin, respectively, inhibited the binding of [3H]GBR 12935, at concentrations which inhibit the uptake of norepinephrine or serotonin.

Animals↗
PubMed1990

Distribution and characterization of VIP-related peptides in the rat spinal cord.

The possible existence in the rat spinal cord of a peptide related to VIP, VIP(22-28), has been evaluated. VIP contains paired basic aminoacid residues at which posttranslational cleavage of these peptides might occur. The lumbo-sacral region of rat spinal cord had the most VIP(22-28)-like immunoreactivity (ir-VIP(22-28]. Chromatographic analysis of spinal extracts showed that ir-VIP(22-28) consisted of two major peaks, one eluting as authentic VIP(1-28) and the other as VIP(22-28). HPLC confirmed these results, revealing the presence of intact VIP(1-28) and two or more less hydrophobic peptides, one of which corresponded to authentic VIP(22-28). The other two components found have not yet been identified. Further studies are necessary to provide information on the biological significance of VIP(22-28).

Animals↗
PubMed1989

Effects of pertussis toxin on opioid regulation of catecholamine release from rat and guinea pig brain slices.

Opioid agonists selective for mu-, delta-, and kappa-receptors are all capable of regulating the stimulated release of noradrenaline from three terminal fields (cortex, hippocampus, and cerebellum) of the noradrenergic projections from locus coeruleus in the guinea pig brain. Intracerebroventricular injections of pertussis toxin abolished the ability of a mu-selective agonist and of a delta-selective agonist to inhibit stimulated noradrenaline release, but left unaffected the concentration-related inhibition of NE release by a kappa agonist. Thus, mu- and delta-receptors have been shown to be coupled to their effector system in these noradrenergic neurons via guanyl nucleotide binding proteins (G proteins) which are sensitive to pertussis toxin, while kappa-receptors in the same neurons appear to be coupled through a different mechanism which is significantly less sensitive to pertussis toxin. In contrast to opioid receptor regulation of noradrenaline release in guinea pig hippocampus, mu-, but not delta- or kappa-agonists are capable of regulation of stimulated noradrenaline release from rat hippocampus and cortex, and kappa-, but not mu- or delta-agonists are capable of inhibiting the stimulated release of dopamine from rat striatum and cortex. Pertussis toxin injections significantly attenuated mu-agonist inhibition of noradrenaline release, but had no effect on the ability of a kappa-selective agonist to regulated dopamine release, confirming the insensitivity of the kappa-receptor-effector coupling system to pertussis toxin.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Morphine-induced desensitization and down-regulation at mu-receptors in 7315C pituitary tumor cells.

Pituitary 7315c tumor cells maintained in culture were treated with varying concentrations of morphine from 10 nM to 300 microM, for periods of five or forty-eight hours. The ability of the mu-opioid receptor agonist, DAMGO, to inhibit forskolin-stimulated adenylyl cyclase in washed membrane preparations from the treated cells was compared with its activity in membranes from cells incubated in the absence of added morphine. In the same membrane preparations, the number and affinity of mu-opioid receptors was estimated by measurements of [3H]diprenorphine binding. After 5 hr of treatment with morphine concentrations of 100 nM or higher, a significant reduction in inhibition of adenylyl cyclase by DAMGO was observed. Little further loss of agonist activity was observed when the incubations were extended to 48 hr. After 5 hr of morphine treatment, there was no change in either the number of receptors, or their affinity for [3H]diprenorphine. However, after 48 hr of morphine treatment, greater than 25% reductions in receptor number were apparent with morphine pretreatment concentrations of 10 microM or higher. These results suggest that opioid tolerance in this system is primarily associated with a reduced ability of agonist-occupied receptor to activate the effector system. Receptor down-regulation was not necessary for loss of agonist response, although a reduction in receptor number occurred after exposure to high concentrations of morphine for periods longer than 5 hr.

Adenylyl Cyclases↗
PubMed1989

Selective opioid antagonist effects on opioid-induced inhibition of release of norepinephrine in guinea pig cortex.

Opioid agonists with selectivity for mu, delta and kappa-receptors have each been shown to inhibit the K+-stimulated release of [3H]norepinephrine (NE) from slices of guinea pig cortex maintained in vitro. In order to provide further evidence that each of these types of opioid receptor can regulate the release of NE in this tissue, experiments with receptor-type selective opioid antagonists have been conducted. In initial experiments, the selectivity of the antagonists for specific types of opioid receptors in the cortex of the guinea pig in an incubation medium of the same composition as that used for release studies was confirmed. The delta-receptor selective antagonist, ICI 174,864, prevented the inhibitory actions of the delta-selective agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE), but had little effect on the inhibitory actions of the mu-selective agonist, Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO), or the kappa-selective agonist, U-50,488H. In contrast, the kappa-selective antagonist, nor-binaltorphimine (nor-BNI) prevented the inhibitory actions of U-50,488H, but had little effect on the inhibitory actions of DPDPE or DAMGO. The greater potency of the partially mu-selective antagonist, naloxone, in reversing the effects of DAMGO relative to those of DPDPE or U-50,488H was confirmed. These results support the conclusion that mu- delta- and kappa-opioid receptors each exert a negative regulatory effect on the stimulated release of NE in the cortex of the guinea pig.

Animals↗
PubMed1989

Selective changes in mu opioid receptor properties induced by chronic morphine exposure.

Chronic infusion of morphine to guinea pigs produced selective changes in mu agonist binding properties in cerebrocortical membrane preparations. Employing the mu-selective opioid agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) in direct binding studies and in competition of labeled antagonist binding, we found that the major changes were a decrease in the number of sites with high affinity for agonist, a small reduction in total receptor number, and a loss in the ability of guanosine 5'-[gamma-thio]triphosphate to regulate binding. A fraction of high-affinity mu receptors appeared to retain their high affinity for agonist and their sensitivity to guanine nucleotide analogue after the induction of morphine tolerance, possibly because the morphine concentrations achieved in brain were insufficient to uncouple all mu receptors from associated guanine nucleotide-binding regulatory proteins. Some membrane preparations were treated with pertussis toxin, which has been shown to functionally uncouple mu opioid receptors from their effector systems. In these preparations, a single agonist-affinity state of the receptor was observed. The apparent dissociation constant for this affinity state in pertussis toxin-treated membranes was similar to the lower-affinity state observed in preparations from morphine-tolerant animals. In contrast to the changes observed at mu opioid binding sites, no significant changes in agonist affinity or binding density were observed for selective delta or kappa agonists, consistent with the development of selective tolerance at mu receptors.

Animals↗
PubMed1988

Multiple agonist-affinity states of opioid receptors: regulation of binding by guanyl nucleotides in guinea pig cortical, NG108-15, and 7315c cell membranes.

Multiple affinity states of opioid receptors of the mu and delta types have been identified in membranes prepared from cells which bear only one type of opioid receptor (mu receptors in 7315c cells, delta receptors in NG 108-15 cells), and in guinea pig cortical membranes where both types of receptors were present in the membrane preparations. States of mu and delta receptors which have agonist affinities too low to be identified by radiolabeled agonist have been measured indirectly by agonist competition for sites labeled by radioactive antagonist. Using analogues of guanyl nucleotides, we have examined the competition of the mu and delta agonists DAGO and DSLET against [3H]DIP or [3H]NAL binding to opioid receptors and identified several agonist affinity states. In the absence of added nucleotide, competition of DSLET for [3H]DIP binding to delta opioid receptors revealed the presence of two binding sites with differing apparent agonist affinities. Addition of GDP beta S produced a steep monophasic curve which was best fit by a one-site model. In contrast, in the presence of added GTP or GTP gamma S, two affinity states were again apparent for DSLET competition at the delta receptor. The competition curve with GTP was shifted to the right relative to that produced in the absence of added guanyl nucleotide, indicating the presence of a lower apparent affinity state than any observed under other treatment conditions. DAGO competed against [3H]DIP or [3H]NAL binding to mu receptors over a wide concentration range in the absence of added guanyl nucleotide, consistent with the occupation by this ligand of more than one agonist affinity state of the mu receptor. However, when GDP beta S was added to the incubation mixture, only a single binding site was identified. Two mu receptor affinity states were again observed in the presence of added GTP or GTP gamma S. One of these had significantly lower apparent affinity than those states detected in the absence of added nucleotide or with GDP beta S. Pertussis toxin treatment resulted in a monophasic agonist competition curve which was best fitted by a single-site model in both 7315c and NG108-15 cell membranes. Addition of 100 microM GTP did not affect the agonist Kapp or Bmax after pertussis toxin treatment, suggesting that sites labeled under these conditions were not functionally associated with a G protein. In general, the effects of guanyl nucleotides were qualitatively similar at mu and delta receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Effects of chronic morphine exposure on opioid inhibition of adenylyl cyclase in 7315c cell membranes: a useful model for the study of tolerance at mu opioid receptors.

The effects of prolonged morphine exposure on the mu opioid receptor in 7315c pituitary tumor cell membranes have been examined. Since a low concentration of naloxone reversed the inhibition of forskolin-stimulated adenylyl cyclase induced by the mu-selective agonist, Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO), and by high concentrations of [D-Pen2-D-Pen5]enkephalin (DPDPE), we suggest that these cells contain a homogeneous population of mu opioid receptors coupled to adenylyl cyclase via a guanyl nucleotide-binding protein. Studies measuring the ability of [D-Ala2-D-Leu5]enkephalin (DADLE), an opioid agonist, to inhibit adenylyl cyclase in cells that had been exposed to 100 microM morphine for varying periods of time, indicated that the agonist no longer inhibited enzyme activity after 5 hr of morphine exposure. Measurements of 3H-antagonist binding in membranes from cells exposed to morphine demonstrated a decreased receptor density after 24 hr of 100 microM morphine exposure with no change in the antagonist affinity. Computer analysis indicated a 20% decrease in the number of mu receptors labeled after 24 hr of morphine exposure and a 60% decrease after 72 hr of exposure. Computer analysis of agonist competition against 3H-antagonist binding confirmed the existence of one binding site with an affinity intermediate between the high and low apparent affinity states observed in membranes from untreated cells. Addition of 10 microM GTP gamma S did not affect the agonist affinity or receptor density in membranes from morphine-treated cells, suggesting that the receptors were uncoupled from G proteins, as observed in 7315c cell membranes that have been treated with pertussis toxin. Thus chronic morphine treatment induced a rapid loss of opioid mu receptor-mediated inhibition of adenylyl cyclase (desensitization), and a more slowly developing reduction in receptor number. The desensitization was accompanied by a loss of guanyl nucleotide regulation of agonist affinity. These findings are comparable to results reported for the delta opioid receptor and the beta-adrenergic receptor upon prolonged agonist exposure.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Kappa receptor regulation of dopamine release from striatum and cortex of rats and guinea pigs.

The effects of opioid agonists with selectivity for kappa, mu and delta types of opioid receptors on the K+-stimulated release of [3H]dopamine (DA) from striatum and cortex of rat and guinea pig loaded previously with the monoamine have been studied. The kappa agonist U50488H did not affect base-line release of [3H]DA measured in 5 mM K+, but produced a dose-dependent inhibition of the release of [3H]DA stimulated by 20 mM K+ from slices of striatum in rat and guinea pig, with an IC50 of about 0.5 nM in each case. In contrast, the mu-selective agonist, Tyr-D-Ala-Gly-(Me)Phe-Gly-ol, and the delta-selective agonist, [D-Pen2-D-Pen5]enkephalin, did not inhibit stimulated release from the slice preparations at concentrations up to 1 microM. The inhibitory effects of U50488H were antagonized by naloxone, and the potent and selective kappa antagonist, nor-binaltorphimine (nor-BNI). Similar results were obtained when release of [3H]DA from rat and guinea pig cortex slices was examined. In guinea pig cortex, the maximum inhibition of DA release induced by U50488H was 80% of control-stimulated fractional release. In rat cortex and in striatum of both species the maximum release was about 40% of control fractional release. Thus, in the guinea pig, the mesocortical dopaminergic pathway appears more sensitive to the inhibitory effects of U50488H than the nigrostriatal system. The effects of the opioids on the K+ (12.5 mM)-stimulated release of [3H]DA from guinea pig striatal synaptosomes also were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Selective tolerance at mu and kappa opioid receptors modulating norepinephrine release in guinea pig cortex.

The development of selective tolerance, that is, a loss in the ability of an agonist to exert an effect without concomitant loss in the ability of an agonist which acts through another receptor type to similarly lose its effectiveness, has provided supporting evidence for the existence of multiple opioid receptor types in brain and peripheral tissues. In brain, this phenomenon has generally been demonstrated for agonists which produce different physiological effects. In this study, we describe selective tolerance at two opioid receptor types which converge upon a single function. The effects of chronic treatment for 6 days with the mu agonist morphine (1.7 mg/kg/hr) and the kappa agonist U50, 488H (300 micrograms/kg/hr) on the ability of mu and kappa opioid agonists to inhibit the stimulated release of [3H]norepinephrine from slices of guinea pig cortex were investigated. Mu, delta and kappa selective agonists have been shown previously to be capable of regulating the stimulated release of norepinephrine. Chronic administration of morphine resulted in a diminution in the ability of the mu agonists Tyr-D-Ala-Gly-N(Me)Phe-Gly-ol, morphine and etorphine, but not of U50, 488H, to inhibit the stimulated release of [3H]norepinephrine. Conversely, chronic U50, 488H infusion decreased the ability of U50, 488H to inhibit release, with no change in the effectiveness of Tyr-D-Ala-Gly-N(Me)Phe-Gly-ol. The degree of tolerance observed for mu agonists in tissue from morphinized animals is discussed with regard to their efficacy and selectivity.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Opioid receptor regulation of the release of norepinephrine in brain.

The ability of opioids to inhibit the release of norepinephrine (NE) from slice preparations of brain has been tested. Slices of brain were preincubated with [3H]NE allowing uptake of the [3H]NE into intraneuronal stores of NE. After rinsing, the tissues were incubated at 37 degrees C in Krebs buffer containing 5mM K+, for estimation of baseline release and then in 20 mM K+ to stimulate release. The [3H]NE released into the incubation medium was increased by blockade of neuronal re-uptake with desipramine and by blockade of alpha 2-adrenoceptors with yohimbine. These agents were used routinely in subsequent incubations. Release was also Ca2+ dependent. Stimulated release of [3H]NE from slices of cortex of the guinea pig and rat was inhibited by the mu opioid receptor agonist, Tyr-D-Ala2-Gly-NMePhe-Gly-ol (DAGO) in a naloxone-reversible manner, although naloxone itself produced a measurable inhibitory effect in the absence of opioid agonist. Stimulated release of [3H]NE from slices of guinea pig cortex was also inhibited by the delta receptor selective peptide, [D-Pen2, D-Pen5] enkephalin (DPDPE), and the kappa receptor selective agent, U50,488H. The inhibitory effect of both agents was reversed by naloxone. In rat cortex, DAGO induced a similar inhibition of release to that seen in guinea pig cortex, but DPDPE and U50,488H were much less effective, producing only weak inhibition even in large doses. Similar results were obtained when effects of opioids on [3H]NE release from hippocampus and cerebellum of the guinea pig and rat were compared. In guinea pig tissues, agonists acting preferentially through mu, delta and kappa receptors were all active in inhibiting stimulated release of [3H]NE, but in hippocampus and cerebellum of the rat, only DAGO inhibited release while DPDPE and U50,488H either had no effect or potentiated the stimulated release. These results suggest that in the rat only mu type opioid receptors mediate an inhibitory regulation of NE release from the cortex, hippocampus and cerebellum terminal projections of locus coeruleus noradrenergic neurons. In the guinea pig, stimulated release of [3H]NE was subject to inhibitory regulation by mu, delta and kappa opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Chromatographic characterization of dynorphin and [Leu5]enkephalin immunoreactivity in guinea pig and rat testis.

Tissues of the reproductive tract have been shown to contain mRNAs coding for pro-opiomelanocortin (POMC), pro-enkephalin and pro-dynorphin. However, the amounts of immunoreactive opioid peptides in these tissues are low, and in the case of the enkephalins and dynorphin, the molecular species responsible for the immunoreactivities have not been characterized. The chromatographic properties of dynorphin and enkephalin immunoreactivities in extracts of guinea pig and rat testis have therefore been determined. Dynorphin A and dynorphin B immunoreactivity was heterogeneous, with a significant amount attributable to high-molecular-weight forms. About 20% of the dynorphin A immunoreactivity, and about 40% of the dynorphin B immunoreactivity, in guinea pig testis extracts behaved as authentic dynorphin A or B, respectively during fractionation by ion exchange, gel filtration and high-performance liquid chromatography. Both high- and low-molecular-weight forms of [Leu5]enkephalin immunoreactivity were also present, with roughly 50-70% of the immunoreactivity attributable to low-molecular-weight forms. In extracts of guinea pig testis only a small part of this immunoreactivity eluted as authentic [Leu5]enkephalin during high-performance liquid chromatography. In rat testis most of the low-molecular-weight [Leu5]enkephalin immunoreactivity behaved as the authentic peptide. These results confirm that opioid peptides are produced in guinea pig and rat testis, and demonstrate that immunoreactive forms of the peptides similar to those found in brain and pituitary are present in the tissue.

Animals↗
PubMed1986

Opioid ligand binding sites in the spinal cord of the guinea-pig.

The properties of opioid binding sites in membranes from the spinal cord of the guinea-pig were analyzed in experiments employing radiolabeled opioid ligands, selective or partially selective for mu, delta and kappa-type binding sites. Incubation was conducted at 37 degrees C in a quasi-physiological modified Krebs medium, containing sodium and magnesium. The types of binding sites were discriminated on the basis of their affinities for [3H-D-Ala2-MePhe4-Gly5-ol]enkephalin ([3H]DAGO), [3H-D-Ala2-D-Leu5]enkephalin, and [3H]ethylketocyclazocine and the relative potencies of the displacing ligands, DAGO, [D-Ser2-Leu5]enkephalyl-Thr and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide methanesulfonate hydrate (U50488H), which are selective for mu, delta and kappa type binding sites respectively. In membranes from whole spinal cord, kappa type sites comprised about 60%, mu about 30% and delta about 10% of the total of mu, delta and kappa binding sites. Binding sites of the mu type were also found in the lumbo-sacral region of guinea-pig spinal cord, in contrast to earlier reports of their absence from this tissue. Morphine showed a better than 500-fold selectivity for mu over kappa sites in spinal cord, while nalbuphine and (-)1-cyclopentyl-5-(1,2,3,4,5,6-hexahydro-8-hydroxy-3,6,11- trimethyl-2,6-methano-3-benzazocin-11-yl)3-pentanone methanesulfonate (WIN 44441-3) showed about a 10-fold selectivity for mu sites. The drug U50488H had about a 150-fold greater affinity for kappa than mu-type binding sites.

Animals↗
PubMed1986

Response of rat pituitary anterior lobe prodynorphin products to changes in gonadal steroid environment.

The total content of rat pituitary anterior lobe (AL) immunoreactive (ir) dynorphin A (ir-Dyn A) and ir-dynorphin B (Dyn B) increased in male rats between 15 and 58 days of age, but there was little alteration in the concentration of ir-Dyn A or B expressed relative to protein content. Adult rats (90 days of age) had lower concentrations of these peptide immunoreactivities in the AL. Castration of 58-day-old male rats produced a testosterone-reversible loss of ir-Dyn A and B by 50-60% 3 days after surgery. Thereafter, the levels of these peptides gradually increased to 2.5 times the levels found in control animals at 1 month after castration. These effects of castration on AL dynorphin were not seen in 15-day-old rats and were much less marked in adults. Similar changes were seen in the levels of other prodynorphin products, alpha- and beta-neo-endorphin (ir-alpha-nEnd and ir-beta-nEnd), and ir-[Leu5]enkephalin (ir-LE). Administration of testosterone (100 micrograms/100 g BW) to castrated rats for 2 days largely prevented the drop in the levels of AL ir-Dyn A and B. Ovariectomy produced an increase in the levels of ir-Dyn A, Dyn B, alpha-nEnd, beta-nEnd, and LE 2 weeks after surgery, but, in contrast to castration, no significant decrease was seen 3 days after ovariectomy. These changes in AL content of dynorphin-related peptides after castration or ovariectomy directly reflect those previously reported for AL content of LH. The mechanisms regulating storage (and perhaps secretion) of AL peptides derived from prodynorphin may be similar to those regulating storage and secretion of LH and FSH in rat AL. AL ir-LE could potentially arise from proenkephalin A or prodynorphin (proenkephalin B). Ir-LE levels in AL were approximately 10 times higher than the levels of ir-[Met5]-enkephalinyl-Arg-Gly-Leu (ME-RGL) in male rat AL, and changes in ir-LE content after castration were very similar to those observed in other prodynorphin-derived peptides, but different from the effects of castration on ir-ME-RGL. It is possible that prodynorphin is a major source of AL ir-LE.

Animals↗