Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We attempted to identify the kyotorphin receptor and the post receptor mechanisms mediated by GTP-binding proteins (G-proteins), using reconstitution techniques. The specific binding of [3H]kyotorphin in rat brain membranes was composed of high affinity (Kd = 0.34 nM) and low affinity (Kd = 9.07 nM) binding. As the high affinity binding disappeared in the presence of guanosine 5'-O-(3-thiotriphosphate) and MgCl2, we investigated the kyotorphin receptor-mediated changes in membrane G-protein activity by measuring low Km GTPase activity. Kyotorphin produced a stimulation of low Km GTPase, and this stimulation was antagonized by Leu-Arg, a synthetic dipeptide which showed a potent displacement of [3H]kyotorphin binding, yet in itself had no effect on the low Km GTPase. The kyotorphin stimulation of low Km GTPase was abolished by pretreating membranes with islet-activating protein, pertussis toxin, and was recovered by reconstitution with purified G-protein, Gi, but not with Go. Similar evidence of selective coupling of kyotorphin receptor to Gi was obtained with the phospholipase C assay. Kyotorphin-induced stimulation of phospholipase C was also abolished by islet-activating protein-treatment and recovered by reconstitution with Gi but not with Go. These findings indicate that specific high and low affinity kyotorphin receptors exist in the rat brain and that the kyotorphin receptor is functionally coupled to stimulation of phospholipase C, through Gi. This study provides the first evidence of a selective involvement of Gi in the receptor-mediated activation of phospholipase C.
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PMID:The kyotorphin (tyrosine-arginine) receptor and a selective reconstitution with purified Gi, measured with GTPase and phospholipase C assays. 253 90

Bradykinin (BK) given into the plantar (i.pl.) of the mouse hind-limb produced a flexor response. The flexor responses were dependent on BK doses (0.02-20 pmol, i.pl.), and were completely abolished by Hoe140, a B2-type BK receptor antagonist. Kyotorphin, an analgesic neuropeptide which shows enkephalin release in brain slices, produced a dose-dependent reduction of the BK-induced nociceptive responses in ranges of 10 pmol to 1 nmol (i.pl.). Such analgesic effects of kyotorphin were reversed by leucine-arginine, a specific kyotorphin receptor antagonist, but not by naloxone. The kyotorphin-analgesia was also abolished by pertussis toxin (PTX) pretreatment. These results suggest that peripheral analgesic effects of kyotorphin are mediated through mechanisms of kyotorphin specific receptor and PTX-sensitive Gi/Go, and that the enkephalin release is not necessary for this analgesia.
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PMID:Peripheral non-opioid analgesic effects of kyotorphin in mice. 940 52