Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The family of the G protein-coupled opioid receptors was recently extended by a novel member that did not bind any of the typical opioid receptor ligands. Identification of the orphan receptor in this way led to the advent of "reverse pharmacology" to identify the corresponding physiological ligands. Nociceptin, a heptadecapeptide, which was discovered as an endogenous ligand, first, attracted us by its reported nociceptive or anti-opioid actions. However, following studies revealed that this peptide has both nociceptive and antinociceptive actions under different conditions; e.g., administration routes or doses affect its actions. In our recent studies using a unique peripheral peripheral nociception test, nociceptin given locally at lower doses was found to produce nociception through substance P release from nociceptor endings, while at higher doses, it produced antinociceptive actions through an inhibition of phospholipase C activity stimulated by nociceptive substances. Such hypothetical mechanisms can be applied to the mechanisms of nociceptin-induced paradoxical actions in the central nervous system. The physiological role of nociceptin has recently been reported using nociceptin receptor knock-out mice. Following the report of a hearing problem in such mice, the nociceptin receptor was found to be involved in the development of morphine analgesic tolerance. In this review, more findings on the physiological roles of nociceptin or its receptor, such as pain control and memory-learning, are discussed on the basis of reports using nociceptin receptor knock-out mice.
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PMID:[Molecular pharmacology and physiology of nociceptin]. 1067 95

Nociceptin is a peptide transmitter belonging to the opioid family. Nociceptin has recently attracted considerable interest since it appears to exhibit a number of differences to the other opioids. In the present study, we used a nociceptin antibody to map the distribution of nociceptin in the human trigeminal ganglion. In addition, we studied the nociceptin receptor at mRNA levels by RT-PCR and the vasomotor response to nociceptin in human cerebral vessels using a sensitive in vitro method. About 70% of all neuronal cells in trigeminal ganglia were nociceptin immunopositive. Nociceptin was predominantly (78%) expressed in medium-sized cells (30-60 microm). Nociceptin also distributed in small-sized cells (14% of positive cell bodies; <30 microm) and in large-sized cells (8% of positive cell bodies; >60 microm). Double immunostaining showed that in the human trigeminal ganglion nociceptin colocalized with calcitonin gene-related peptide (CGRP), substance P (SP), nitric oxide synthase (NOS) or pituitary adenylate cyclase activating peptide (PACAP). About 61% of nociceptin positive cells contained CGRP, 54% contained SP, 50% contained NOS and 68% contained PACAP. Immunoreactivity to nociceptin was not detected in human cerebral blood vessels. Reverse transcriptase-polymerase chain reaction detected the expression of nociceptin receptor mRNA in trigeminal ganglia but not in basilar arteries. To further examine whether there are functional nociceptin receptors in human cerebral arteries, a pharmacological study was done, where cerebral arteries revealed strong contractions to 60 mM K(+) and U466166 and strong relaxation to CGRP. Nociceptin failed to elicit contraction or relaxation. In conclusion, nociceptin is expressed in human trigeminal ganglia but not in cerebral blood vessels. Nociceptin is colocalized with CGRP, SP, NOS and PACAP. Nociceptin receptor mRNA is expressed in human trigeminal ganglia but not in basilar arteries. The functional role of nociceptin may be at the presynaptic level.
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PMID:Nociceptin immunoreactivity and receptor mRNA in the human trigeminal ganglion. 1257 78

Recent evidence suggests a role of prepronociceptin/orphanin FQ (preproN/OFQ) derived neuropeptides in nociceptive signaling. Here, we examined the expression of preproN/OFQ and the nociceptin receptor ORL1 (opioid receptor like receptor 1) in the dorsal root ganglion (DRG) of the rat in relation to that of substance P (SP) and calcitonin gene-related peptide (CGRP). Double labeling in situ hybridization revealed a constitutive expression of preproN/OFQ in a distinct minor subpopulation of very small DRG neurons with no evidence for coexpression with either SP or CGRP. However, a major subpopulation of the preproN/OFQ-positive neurons showed direct juxtaposition to SP and CGRP containing neurons. ORL1 was abundantly expressed with a high degree of coexpression with SP (72%) and CGRP (82%) suggesting that N/OFQ may presynaptically modulate primary sensory nociceptive signaling. The DRG cell line F11 was found to express preproN/OFQ, but not ORL1, and, therefore, is well suited to study the mechanisms of N/OFQ gene regulation in vitro.
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PMID:Relationship of pronociceptin/orphanin FQ and the nociceptin receptor ORL1 with substance P and calcitonin gene-related peptide expression in dorsal root ganglion of the rat. 1293 25