Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GPR7 and GPR8 are two structurally related orphan G protein-coupled receptors, presenting high similarities with opioid and somatostatin receptors. Two peptides, L8 and L8C, derived from a larger precursor, were recently described as natural ligands for GPR8 (Mori, M., Shimomura, Y., Harada, M., Kurihara, M., Kitada, C., Asami, T., Matsumoto, Y., Adachi, Y., Watanabe, T., Sugo, T., and Abe, M. (December, 27, 2001) World Patent Cooperation Treaty, Patent Application WO 01/98494A1). L8 is a 23-amino acid peptide, whereas L8C is the same peptide with a C terminus extension of 7 amino acids, running through a dibasic motif of proteolytic processing. Using as a query the amino acid sequence of the L8 peptide, we have identified in DNA databases a human gene predicted to encode related peptides and its mouse ortholog. By analogy with L8 and L8C, two peptides, named L7 and L7C could result from the processing of a 125-amino acid human precursor through the alternative usage of a dibasic amino acid motif. The activity of these four peptides was investigated on GPR7 and GPR8. In binding assays, L7, L7C, L8, and L8C were found to bind with low nanomolar affinities to the GPR7 and GPR8 receptors expressed in Chinese hamster ovary (CHO)-K1 cells. They inhibited forskolin-stimulated cAMP accumulation through a pertussis toxin-sensitive mechanism. The tissue distribution of prepro-L7 (ppL7) and prepro-L8 (ppL8) was investigated by reverse transcription-PCR. Abundant ppL7 transcripts were found throughout the brain as well as in spinal cord, spleen, testis, and placenta; ppL8 transcripts displayed a more restricted distribution in brain, with high levels in substantia nigra, but were more abundant in peripheral tissues. The ppL7 and ppL8 genes therefore encode the precursors of a class of peptide ligands, active on two receptor subtypes, GPR7 and GPR8. The distinct tissue distribution of the receptor and peptide precursors suggest that each ligand and receptor has partially overlapping but also specific roles in this signaling system.
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PMID:Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8. 1240 9

The human 7-transmembrane receptor GPR7 has sequence similarity to opioid and somatostatin receptors, and can be activated by the recently discovered neuropeptides NPB and NPW. This receptor is highly expressed in the nervous system, with suggested roles in neuroendocrine events and pain signaling. In this study, we investigated whether the GPR7 receptor is expressed in the peripheral nervous system under normal and pathological conditions. A low level of GPR7 receptor was observed in myelin-forming Schwann cells in both normal human and rat nerve, and in primary rat Schwann cell cultures. Peripheral nerve samples taken from patients exhibiting inflammatory/immune-mediated neuropathies showed a dramatic increase of GPR7 receptor expression restricted to myelin-forming Schwann cells. Complementary animal models of immune-inflammatory and ligation-induced nerve injury and neuropathic pain similarly exhibited an increased myelin-associated expression of GPR7 receptor. These results suggest a relationship between the pathogenesis of inflammatory/immune-mediated neuropathies, GPR7 receptor expression, and pain transmission.
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PMID:Schwann cell overexpression of the GPR7 receptor in inflammatory and painful neuropathies. 1560 41

Neuropeptide W-23 (NPW23) is an endogenous ligand of both GPR7 and GPR8, and neuropeptide B (NPB) is an endogenous ligand of GPR7. GPR7 mRNA has been detected in regions of the cortex, the hippocampus, the hypothalamus, and the spinal cord in the rat, but GPR8 has not been found in rodents. GPR7 and GPR8 receptors have structural features in common with both opioid and somatostatin receptors. The effects of intrathecal (i.t.) application of NPW23 and NPB were tested in two inflammatory pain models (plantar injection of formalin or carrageenan) and two thermal nociceptive tests (52.5 degrees C and 50.5 degrees C hot plates) and one mechanical nociceptive test in the rat. I.t. injection of either NPW23 or NPB decreased the number of agitation behaviors induced by paw formalin injection and attenuated the level of mechanical allodynia, but not the level of thermal hyperalgesia, induced by paw carrageenan injection in a dose-dependent manner at a dose between 0.1 and 10 microg, significantly. The effects of either 10 microg of NPW23 or 10 microg of NPB were not antagonized by 10 microg of naloxone. I.t. injection of either NPW23 or NPB had no effect in both the 52.5 degrees C hot plate test or in the 50.5 degrees C hot plate tests at a dose between 1 and 100 microg. I.t. injection of either 10 microg of NPW23 or 10 microg of NPB had no effect in the mechanical nociceptive test. I.t. injection of either 10 microg of NPW23 or 10 microg of NPB significantly suppressed the expression of Fos-like immunoreactivity of the L4-5 spinal dorsal horn induced by paw formalin injection. These data suggest that both spinally-applied NPW23 and NPB suppressed the input of nociceptive information to the spinal dorsal horn, produced an analgesic effect in the formalin test, and attenuated the level of mechanical allodynia in the carrageenan test, and that either spinally applied NPW23 or spinally applied NPB had no effect in the physiological condition.
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PMID:Anti-hyperalgesic effects of intrathecally administered neuropeptide W-23, and neuropeptide B, in tests of inflammatory pain in rats. 1591 Jul 67

Neuropeptide W-23 and neuropeptide B are each an endogenous ligand of GPR7. GPR7 mRNA has been detected in regions of the cortex, the hippocampus, the hypothalamus and the spinal cord in the rat. GPR7 receptor has structural features in common with both opioid and somatostatin receptors. In the present study, the effects of intrathecal and i.c.v. application of neuropeptide W-23 and neuropeptide B on the level of mechanical allodynia induced by partial sciatic nerve ligation were tested in rats. The level of mechanical allodynia was measured using von Frey filaments. Intrathecal injection of either neuropeptide W-23 or neuropeptide B attenuated the level of mechanical allodynia in a dose dependent manner at a dose between 0.1 and 10 microg, but i.c.v. injection of either neuropeptide W-23 or neuropeptide B had no effect on the level of mechanical allodynia at a dose between 3 and 30 microg. The effect of intrathecal administration of either 10 microg of neuropeptide W-23 or 10 microg of neuropeptide B was not antagonized by i.p. injection of 1 mg/kg of naloxone. Immunohistochemical examination revealed that neuropeptide W-23 was expressed mainly in the small- to medium-sized neuronal profiles in the dorsal root ganglion and that partial sciatic nerve injury decreased the percentage of neuropeptide W-23-like immunoreactivity positive neuronal profiles that were labeled by IB4. These data suggest that neuropeptide W-23 is involved in the nociceptive transmission in spinal cord and that both spinally-applied neuropeptide W-23 and spinally-applied neuropeptide B produce anti-allodynic effects in the partial sciatic nerve ligation model in rat.
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PMID:Effects of intrathecal and i.c.v. administration of neuropeptide W-23 and neuropeptide B on the mechanical allodynia induced by partial sciatic nerve ligation in rats. 1628 88

Neuropeptide W (NPW) is a regulatory peptide that acts via two subtypes of G protein-coupled receptors, GPR7 and GPR8. Evidence has been provided that NPW is involved in the central regulation of energy homeostasis and feeding behavior. In this study, we examined the effects of NPW on insulin release and localization of NPW in the rat pancreas. NPW (10-100 nM) significantly increased insulin release in the presence of 8.3 mM, but not 2.8 mM, glucose in the isolated rat islets. By fura-2 microfluorometry, NPW (1-100 nM) concentration-dependently increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) at 8.3 mM glucose in rat single beta-cells. The NPW-induced [Ca(2+)](i) increase was abolished under external Ca(2+)-free conditions and by an L-type Ca(2+) channel blocker nifedipine (10 microM). RT-PCR analysis revealed that mRNA for NPW was expressed in the rat pancreas and hypothalamus. Double immunohistochemical analysis showed that NPW-immunoreactivity was found in islets and co-localized with insulin-containing beta-cells, but not glucagon-containing alpha-cells and somatostatin-containing delta-cells. These results suggest that NPW could serve as a local modulator of glucose-induced insulin release in rat islets. NPW directly activates beta-cells to enhance Ca(2+) influx through voltage-dependent L-type Ca(2+) channels and potentiates glucose-induced insulin release.
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PMID:Neuropeptide W in the rat pancreas: potentiation of glucose-induced insulin release and Ca2+ influx through L-type Ca2+ channels in beta-cells and localization in islets. 1786 32

Neuropeptide W (NPW) is a ligand of the recently deorphaned receptor GPR7. Intracerebroventricular injection of this peptide results in reduced serum growth hormone concentration. Using whole-cell patch clamp recordings from somatostatin (SS) neurons in the hypothalamic arcuate nucleus, identified post-hoc using single-cell RT-PCR, we investigated the effects of NPW on membrane excitability. NPW application in acute slices of the arcuate nucleus resulted in the depolarization of the majority (62.5%) of the SS neurons tested, while smaller proportions of cells showed hyperpolarization or no response. Both the depolarization and hyperpolarization of arcuate SS neurons were preserved during recordings where voltage-gated sodium channels were blocked with tetrodotoxin, suggesting direct effects of NPW on the excitability of SS neurons. The observed depolarization of the majority of the SS neurons tested suggests that the central effects of NPW to inhibit growth hormone release results from activation of arcuate SS neurons, which could result in an inhibition of GHRH-releasing neurons.
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PMID:Neuropeptide W influences the excitability of neurons in the rat hypothalamic arcuate nucleus. 1828 80