Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioids, acting via G-protein coupled membrane receptors, induce analgesia. However their role is not limited to their anti-nociceptive action. They are found in several peripheral tissues acting as negative regulators of cellular processes. Even though that is not fully elucidated, it becomes obvious that opioids exert their effects in close relation to other neuropeptides such as somatostatin. Hepatocellular carcinoma is one tumor, among others, which secrete bioactive peptides while somatostatin analogs exert an inhibitory effect. We have used the human hepatocyte-derived cancer cell line HepG2, in order to examine the effect of opioids on cell growth and their possible mode of action. Our results show that the opioid ethylketocyclazocine (EKC) inhibits cell proliferation and induces apoptosis. This inhibitory effect is not exerted via opioids receptors since it was not reversed by the opioid antagonist diprenorphine and functional opioid receptors were not found on HepG2 cells. On the contrary, we show that EKC binds to somatostatin receptors, and activates a PTP signalling cascade. In this respect, the interaction of opioids with somatostatin receptors on hepatocellular carcinoma cells, and the fact that they are widely used for pain control, may provide some additional clues for the discrepancies during treatment with somatostatin analogues.
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PMID:The inhibitory effect of opioids on HepG2 cells is mediated via interaction with somatostatin receptors. 1711 72

Protein tyrosine phosphatase 1B (PTP1B) has been shown to dephosphorylate and inactivate insulin receptors, which contributes to the pathogenesis of diabetes. Neuropathic pain is one of the severe complications that results from diabetic neuropathy. However, whether PTP1B was involved in the development of diabetic neuropathic pain is largely unknown. The current study illustrated that PTP1B was located in spinal cord dorsal horn neurons of Sprague-Dawley rats. Western blot analysis demonstrated that the diabetic neuropathic pain induced by intraperitoneal injection of streptozotocin was associated with an increased protein expression and a dynamic redistribution of spinal PTP1B into excitatory glutamatergic synapses. We found that PTP1B operated to stimulate Src kinase and enhance the tyrosine phosphorylation of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. The siRNA-mediated knockdown of PTP1B in streptozotocin-injected rats repressed Src activity, decreased NMDA receptor phosphorylation and alleviated the thermal hyperalgesia and mechanical allodynia. A similar analgesia against diabetic neuropathic pain was also achieved when PTP1B activity was manipulated by a chemical PTP Inhibitor or PTP1B(C215S) mutant. These data revealed a regulated expression of PTP1B in spinal cord dorsal horn of rats after diabetic neuropathy, and demonstrated that inhibition of PTP1B was beneficial for the treatment of pain hypersensitivity related to diabetes.
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PMID:Inhibition of protein tyrosine phosphatase 1B in spinal cord dorsal horn of rats attenuated diabetic neuropathic pain. 2952 16