Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MOR-1 encodes a mu receptor. In an effort to establish the relationship of this cloned opioid receptor with ingestive behavior and analgesia in rats, the present study examined the actions of four antisense oligodeoxynucleotides aimed at exons 1 (AS1), 2 (AS2), 3 (AS3) and 4 (AS4) of the MOR-1 clone, as well as a mismatch antisense sequence (MS1). Rats were administered intracerebroventricular injections (10 micrograms/2 microliters) of each of the oligodeoxynucleotides on days 1, 3 and 5. Body weight and spontaneous food and water intake were monitored daily. In addition, 2-deoxy-D-glucose (2DG)-induced hyperphagia, central Angiotensin II (ANG-II) induced hyperdipsia and central morphine analgesia were examined 24 h following the last antisense injection. AS1, AS2, AS3 and AS4 each significantly reduced body weight (7-17 g), food intake (8-13 g) and water intake (11-23 ml), while the vehicle or MS1 conditions significantly increased weight (9-20 g) and produced smaller reductions (2-4 g) in food intake. None of the AS probes altered the magnitude of either 2DG-induced hyperphagia or ANG-II-induced hyperdipsia. Central morphine analgesia was reduced by pretreatment with AS1 and AS4, but not AS2, AS3 or MS1. The sensitivity of general feeding to all four exons suggest that the receptor responsible for this action is encoded by the MOR-1 clone. The differences between feeding and morphine analgesia raise the possibility that these two actions are mediated through different mu receptor subtypes. Our results also demonstrate the viability of the in vivo antisense technique in modulating opioid-mediated ingestive responses.
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PMID:Antisense oligodeoxynucleotides against the MOR-1 clone alter weight and ingestive responses in rats. 878 66

The mu opioid receptor mediates ingestive behavior: mu-selective agonists stimulate food intake and antagonists reduce intake in many ingestive situations. Antisense oligodeoxynucleotides directed against each of the four exons of the MOR-1 clone were equally effective in reducing spontaneous food intake and body weight in rats. However, antisense probes directed against only exon 1 or 4 of the MOR-1 clone reduced mu-mediated analgesia. The present study examined whether central administration of antisense probes directed against each of the four exons of the MOR-1 clone or a missense control altered hyperphagia elicited by the mu agonist DAMGO across a range of doses. Antisense probes directed against only exon 1 or 4 blocked hyperphagia at agonist doses of 0.5 and 1.0 microg; this pattern was identical to that observed for mu-mediated analgesia. A missense control failed to exert significant effects, which suggests specificity of antisense actions. The effective antisense probes failed to reduce hyperphagia at a higher (5 microg) agonist dose, a result consistent with limitations in down-regulation of receptor proteins by antisense. The mu antagonist beta-funaltrexamine produced a similar pattern of effects on mu-mediated hyperphagia. The selective actions of antisense probes directed against different exons of the MOR-1 clone in reducing hyperphagia induced by DAMGO suggest that multiple splice variants of the MOR-1 clone exist and raise the possibility of further opioid receptor subclassifications.
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PMID:Antisense mapping of the MOR-1 opioid receptor clone: modulation of hyperphagia induced by DAMGO. 931 53

Antisense oligodeoxynucleotides (AS ODNs) directed against exons 1 and 2 of the MOR-1 clone significantly and markedly reduced (81-93%) hyperphagia induced by the anti-metabolic glucose analogue, 2-deoxy-d-glucose (2DG) across a 4 h time course. AS ODNs directed against exons 3 or 4 of the MOR-1 clone had a more limited (1-2 h) duration of action upon 2DG-induced hyperphagia. 2DG-induced hyperphagia was significantly reduced by AS ODNs directed against exon 2 (44-51%), but not exons 1 or 3 of the KOR-1 clone across a 4 h time course. Whereas an AS ODN probe directed against the KOR3/ORL-1 clone produced small (36%), but significant reductions in 2DG-induced hyperphagia, an AS ODN probe directed against the DOR-1 clone was ineffective. These data provide further converging evidence for the roles of primarily mu, but also kappa1 and kappa3 opioid receptors in mediating the hyperphagic effects of glucoprivation.
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PMID:Antisense mapping of opioid receptor clones: effects upon 2-deoxy-D-glucose-induced hyperphagia. 962 75

Opiate drugs such as morphine stimulate food intake in rats. The morphine metabolite, morphine-6beta-glucuronide (M6G), is more active than morphine in analgesic assays, and appears to act through distinct receptors. Thus, although morphine analgesia is decreased by antisense oligodeoxynucleotides (AS ODNs) targeting exons 1 and 4 of the MOR-1 clone, M6G analgesia is reduced by probes targeting exons 2 and 3 of the MOR-1 clone. Our study examined whether central administration of M6G increased food intake in rats, and characterized this response using either selective mu, kappa1, delta1 and delta2 antagonists, or antisense directed against the various cloned opioid receptors. Central M6G (10-1000 ng) significantly and dose-dependently increased intake after 4 hr. Whereas mu antagonism with betaFNA significantly and dose-dependently reduced M6G-induced hyperphagia, equimolar doses of delta1, delta2, and kappa1 antagonists were ineffective. AS ODNs directed against either exons 2 or 3 of the MOR-1 clone blocked M6G-induced hyperphagia, whereas either AS ODNs directed against exons 1 or 4, or a MS ODN directed against exon 2 were ineffective. In contrast, an AS ODN probe directed against exon 1, but not exon 2, of the MOR-1 clone reduced morphine-induced hyperphagia, an effect identical to DAMGO-induced hyperphagia. Whereas M6G-induced hyperphagia was insensitive to antisense probes directed against the DOR-1, KOR-1 and KOR-3/ORL1 clones, these probes respectively reduced hyperphagia induced by deltorphin II, U50488H and nociceptin. Although pharmacological data indicate that M6G-induced hyperphagia acts through mu receptors, antisense data imply that the hyperphagic actions of M6G are mediated by a receptor distinct from traditional mu agonists, either as an alternative splice variant of the MOR-1 clone or a distinct gene.
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PMID:Morphine-6beta-glucuronide-induced hyperphagia: characterization of opioid action by selective antagonists and antisense mapping in rats. 980 78