Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the D2 agonist B-HT 920 was examined on three behavioural models of induced grooming in the rat. B-HT 920 potently inhibited the grooming elicited by a novel environment, whereas it stimulated the stretching-yawning syndrome. Pretreatment with the selective dopamine D2 receptor antagonist, sulpiride, reversed the phenomenon. When B-HT 920 was administered to rats before water immersion, it similarly antagonized total grooming; wet-dog shakes, detected in these same animals, were potently inhibited. Finally, B-HT 920 displayed inhibitory activity towards adrenocorticotropin hormone-induced excessive grooming. On the basis of these effects, the role of D2 receptor subtypes in the modulation of grooming is discussed.
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PMID:Suppressive effect of the dopamine D2 receptor agonist B-HT 920 on rat grooming. 135 27

1. Intracellular and whole-cell recordings were made from primary cultures of rat intermediate pituitary cells; beta-endorphin secretion was also measured by radioimmunoassay. The effects of dopamine receptor activation on hormone secretion, calcium currents and resting potassium conductance were compared. 2. Spontaneous sodium-dependent action potentials occurred in 82% of cells recorded with intracellular microelectrodes and 64% of cells recorded with whole-cell patch electrodes; the same proportion of cells showed spontaneous calcium-dependent depolarizations in the presence of tetrodotoxin. 3. Calcium currents recorded from holding potentials of -90 or -70 mV showed transient and sustained components, both of which activated at -40 mV and had similar current-voltage relations. Bay K 8644 (1 microM) increased both components by about 130% while nifedipine (1-10 microM) decreased them by a maximum of 30%. Nickel (500 microM) inhibited transient and sustained components by 68 and 50%; cadmium (100 microM) abolished the current. omega-Conotoxin (1 microM) reversibly inhibited the transient component by 26%. 4. The dopamine D2 receptor agonist, quinpirole (0.1-10 microM) inhibited transient and sustained components in all cells by a maximum of 40 and 25% respectively. Quinpirole did not alter the time course of the current. 5. Quinpirole (1-100 nM) hyperpolarized 90% of cells from which intracellular recordings were made and 55% of cells recorded from with whole-cell patch pipettes. Maximum hyperpolarization of 16 +/- 4 mV from a resting potential of -44 +/- 5 mV was observed with 100 nM-quinpirole; concentration producing half-maximal effect was 3 nM. The hyperpolarization resulted from an increase in potassium conductance. 6. Quinpirole (1-100 nM) decreased basal beta-endorphin secretion by 55% and abolished secretion stimulated by Bay K 8644 or isoprenaline; concentrations producing half-maximal inhibitions were 5-10 nM. Tetrodotoxin (1 microM), nifedipine (1 microM), nickel (500 microM) and cadmium (100 microM) did not alter basal or stimulated secretion although higher concentrations of cadmium did inhibit stimulated hormone release. 7. Pertussis toxin pre-treatment prevented all actions of quinpirole. 8. Thus, concentrations of quinpirole that abolished stimulated hormone secretion did not alter calcium currents; conversely, concentrations of calcium channel blockers that partially or completely inhibited calcium currents did not alter basal or stimulated secretion. These results may indicate that calcium influx through the voltage-dependent calcium channels measured in these experiments does not contribute significantly to hormone release from melanotrophs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopamine actions on calcium currents, potassium currents and hormone release in rat melanotrophs. 171 75

REM sleep deprivation induced by means of the platform technique (72 h) was followed by a period of latency to sleep characterized by a marked excitement in rats. The administration of naloxone at the end of the REM deprivation period reduced this latency to sleep while morphine, beta-endorphin and DADLE prolonged it. The dopamine D1 receptor antagonist SCH 23390 was extremely potent (0.003 mg/kg) to reduce the latency to sleep and the excitement while the D1 agonist SKF 38393 induced an opposite effect. The dopamine D2 receptor antagonist L-sulpiride was inactive up to a dose of 25 mg/kg. These data suggest that hyperactivity of the opioid and dopamine systems (specifically mediated through D1 receptors) is involved in such behaviour.
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PMID:Stress-induced insomnia: opioid-dopamine interactions. 289 86

Short-term in vitro incubation of hypothalamo-hypophyseal tissue from young rats was undertaken to discern more clearly the functional relationship between putative dopaminergic neural projections in the pars intermedia and the secretory activity of melanophore stimulating hormone (MSH). This explant consisted of a portion of the mediobasal hypothalamus containing the dopamine neurone cell bodies of interest, with the attached pituitary neuro-intermediate lobe (n.i.l.). The n.i.l. was inserted into the end of a 1 mm diameter tube attached to a perfusion pump which allowed uninterrupted sampling of medium neighbouring the n.i.l. A 'real-time' analysis of hormone secretion was obtained by immediately and continuously bioassaying for MSH. A bipolar stimulating electrode was placed on the ventral floor of the mediobasal hypothalamus either directly on the arcuate nucleus, median eminence or infundibular stalk. Electrical stimulation for 5 min (0.1-20.0 Hz) caused a transient inhibition of basal MSH secretion, while continuous stimulation (0.1-5.0 Hz) led to a much greater, long-term, reversible inhibition. In the latter, the degree of inhibition was generally dependent on stimulation rate up to a maximum at 5 Hz. Application of the dopamine D2 receptor antagonist, 1-sulpiride (0.001-0.1 microM) to the perfusion medium not only completely and reversibly blocked the stimulus-induced inhibition of MSH release but by itself, significantly increased the basal secretion rate. Applied to the isolated n.i.l., 1-sulpiride did not alter release but did prevent the inhibitory response caused by exogenously applied dopamine (0.1 microM). The gamma-aminobutyric acid receptor antagonist, bicuculline (0.01-1.0 microM), had no effect on any of the parameters studied. In explants, cutting the infundibular stalk linking the mediobasal hypothalamus with the n.i.l., mimicked the effects of 1-sulpiride by interrupting impulse flow to the gland. Thus, electrical stimulation of hypothalamic neurones in these explants apparently causes a release of dopamine from nerve terminals in the pars intermedia to inhibit MSH secretion and perhaps other pro-opiomelanocortin-derived peptides as well.
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PMID:The hypothalamo-hypophyseal rat explant in vitro: endocrinological studies of the pars intermedia dopaminergic neural input. 395 80

The present study was undertaken to investigate whether beta-adrenoceptors are involved in regulation of yawning responses to oxytocin and alpha-melanocyte-stimulating hormone (alpha-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. alpha-MSH (20 micrograms/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M1 receptor agonist, administered ICV at a lower dose of 100 micrograms/rat and subcutaneously (SC) at doses of 0.25-2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by alpha-MSH (20 micrograms/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)5,Tyr(Me)2,Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, alpha-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a mucarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and alpha-MSH is modulated by beta-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.
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PMID:Involvement of beta-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and alpha-melanocyte-stimulating hormone, in rats. 761 71

The neuroendocrine profile of the serotonin 5-HT1A receptor agonist and potential anxiolytic drug (+)-4[N-(5-methoxy-chroman-3-yl)N-propylamino]butyl-8-azaspiro-(4, 5)-decane - 7,9-dione (S-20499) was examined in conscious male rats. S-20499 (0.01-20 mg/kg i.p.) dose-dependently elevated plasma adrenocorticotropin (ACTH) and corticosterone concentrations, with maximal effects observed at 15-30 and 30-60 min respectively. S-20499 also reduced plasma prolactin concentration, and did not alter plasma renin activity. S-20499 (1 mg/kg i.p.) also reduced blood pressure and heart rate within 10 min, suggesting reduced sympathetic output. Pretreatment with the 5-HT1A receptor antagonists (-)-pindolol (0.3 mg/kg i.p.) or spiperone (0.01 or 3 mg/kg s.c.) significantly attenuated the stimulatory effects of S-20499 on plasma ACTH and/or corticosterone concentrations. The data suggest that S-20499 stimulates the hypothalamic-pituitary adrenal axis by activating 5-HT1A receptors, although activation of dopamine D2 receptors may contribute to these responses. Like other 5-HT1A receptor agonists, S-20499 does not increase renin secretion. Additionally, it reduces prolactin secretion, presumably by acting as a weak dopamine D2 receptor agonist in the pituitary.
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PMID:Neuroendocrine profile of the potential anxiolytic drug S-20499. 776 66

In the present study, we determined the effects of dopamine receptor agonists and antagonists on basal and ethanol-modulated beta-endorphin (beta-EP) secretion from hypothalamic neurons in primary cultures. Treatment with various concentrations of dopamine D1 agonist SKF 38393 and D1 antagonist SCH 23390 did not affect basal IR-beta-EP release. However, dopamine D2 receptor agonist LY 141865 reduced basal immunoreactive (IR)-beta-EP release in a concentration dependent manner. D2 receptor antagonist, sulpiride, on the other hand, stimulated basal IR-beta-EP release and blocked LY 141865-induced inhibition of IR-beta-EP release in a concentration dependent manner. When the actions of these DA receptor agents on ethanol-modulated IR-beta-EP release were studied, both D1 and D2 receptor agents failed to affect ethanol-modulated IR-beta-EP release. These data suggest that the endogenous secretion of beta-EP from hypothalamic neurons is under the influence of an inhibitory dopaminergic system involving the D2 receptor. Furthermore, ethanol's effects on beta-EP secretion are not mediated by dopamine.
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PMID:Effects of dopamine D1 and D2 receptor agonists and antagonists on basal and ethanol-modulated beta-endorphin secretion from hypothalamic neurons in primary cultures. 874 17

Dopamine negatively regulates POMC gene expression in melanotrophs of the intermediate lobe of the pituitary gland. The dopaminergic receptor involved in this control is the dopamine D2 receptor (D2R). The principal products of the POMC gene in melanotrophs are beta-endorphin and alpha-MSH. POMC is differently processed in the corticotrophs, where it is not regulated by dopamine and it is principally processed into ACTH. Here we show that D2R-deficient mice have increased POMC expression and intermediate lobe hypertrophy. Strikingly, D2R-deficient mice have unexpected elevated ACTH levels with a corresponding increase of corticosteroids and consequent hypertrophy of the adrenal gland. This phenotype is reminiscent of Cushing's syndrome in humans. Interestingly, we show that the elevation in ACTH levels is due to an aberrant processing of POMC in melanotrophs. Indeed, we demonstrate that in addition to controlling POMC gene expression in these cells, dopamine, by modulating the expression of the convertases involved in the cleavage of the POMC prohormone, strictly regulates its processing. These results reveal a key role for dopamine in the control of POMC-derived peptides and furthermore indicate an implication of the dopaminergic system in the genesis of Cushing's syndrome.
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PMID:Absence of dopaminergic control on melanotrophs leads to Cushing's-like syndrome in mice. 971 39

Grooming behavior in rodents has long been related to dopamine receptors in the brain. However, the relative contribution of dopamine D1-like receptors (D1 and D5) and D2-like receptors (D2, D3 and D4) in this behavior has not been established yet. Spontaneous novelty-induced grooming (as assessed with a 30-min sampling test) was reduced in knockout mice lacking the dopamine D1, receptor. Furthermore, the intracerebroventricular (i.c.v.) injection of small quantities of oxytocin, prolactin or the adrenocorticotrophic hormone 1-24 fragment, ACTH-(1-24) was followed by a diminished level of novelty-induced excessive grooming. These neuropeptides caused a sustained increase in grooming level of control animals (wild type). Interestingly, the i.c.v. injection of beta-endorphin enhanced novelty-induced grooming to a level similar in control and knockout mice. The systemic administration of the dopamine D2 receptor antagonist, sulpiride did not suppress the residual grooming activity shown by animals injected with oxytocin, prolactin or ACTH-(1-24), and did not change the behavioral expression of those injected with beta-endorphin. In contrast, the systemic administration of the opioid receptor antagonist, naloxone, totally suppressed the residual grooming activity of oxytocin-, prolactin- or ACTH-(1-24)-injected mice and of those treated with beta-endorphin. In contrast with the behavioral deficit observed in dopamine D1 receptor-deficient mice, dopamine D2 receptor-null animals showed a normal expression of spontaneous novelty-induced grooming and a high level of grooming activity induced by i.c.v. injection of oxytocin, prolactin, ACTH-(1-24) or beta-endorphin. Again, the peripheral injection of naloxone was followed by a suppression of neuropeptide-induced excessive grooming in these animals. These data suggest that dopamine D1 receptors are involved in the expression of novelty-induced grooming in mice. In contrast, dopamine D2 receptors seem not to be important for the expression of this behavior. Furthermore, neuropeptide-enhanced grooming involves dopamine D1, but not dopamine D2 receptors. However, neurotransmitters other than dopamine (e.g., endorphins) may play a supplementary role in neuropeptide-enhanced grooming in mice.
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PMID:The expression of neuropeptide-induced excessive grooming behavior in dopamine D1 and D2 receptor-deficient mice. 998 94

Because alcoholism is a multi-factorial psychiatric disorder, with both psychosocial and biochemical/genetic factors leading to its manifestation in any one individual, the presence of biochemical/genetic factors alone may not lead to the manifestation of the disorder. There are numerous difficulties associated with identification of a trait abnormality in a disorder that requires suitable socio-cultural permissiveness with distinct behavioural characteristics to manifest a disorder that may not require that predisposing trait abnormality in order to develop. Numerous studies have been performed in the past to potentially identify a biochemical or genetic trait abnormality in alcoholism, and not all of them have addressed significant methodological flaws in this type of research. This review addresses some of the difficulties inherent in this research, and aims for a comprehensive review of the highlights of the search for a clinically useful trait abnormality. Some series of investigations hold promise that a trait marker for a particular subset of alcoholics may be developed, e.g. severe alcoholism and the dopamine D2 receptor gene; the level of reaction to alcoholism in family history-positive alcoholics; beta-endorphin abnormalities in specific family groups of alcoholics; reduced P3 wave event-related potentials as markers and predictors of development of substance abuse in predisposed youths; reduced growth hormone response to apomorphine as a predictor of relapse to alcoholism in early abstinence; abnormal adenylyl cyclase activity in certain defined subgroups of alcoholics; and abnormal platelet monoamine oxidase levels in subjects with a behavioural predisposition to addictive disorders. The review concludes that while there has not yet been an identification of a comprehensive trait marker for alcoholism, there is hope for identification subgroups of alcoholics with consistent biological markers within that subgroup that may well prove fruitful over time. It will then be up to a future generation of clinicians to take that information and develop prevention programmes that can incorporate this information to help the predisposed individual avoid alcohol problems.
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PMID:Trait markers for alcoholism: clinical utility. 1052 6


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