Tags

Type your tag names separated by a space and hit enter

Morphological characterization of rat Mas-related G-protein-coupled receptor C and functional analysis of agonists.
Neuroscience. 2008 Jan 02; 151(1):242-54.N

Abstract

A recently described family of "orphan" receptors, called Mas-related G-protein-coupled receptors (Mrg), is preferentially expressed in small nociceptive neurons of the rodent and human dorsal root ganglia (DRG). Mrg are activated by high affinity peptide fragments derived from the proenkephalin A gene, e.g. BAM22 (bovine adrenal medullary). To study the histological distribution and functional properties of these receptors, we combined confocal immunohistochemistry in rat DRG and dermis whole mounts, using new antibodies against the rat Mas-related G-protein-coupled receptor C (MrgC), with single-fiber recordings and neurochemical experiments using isolated hind-paw skin and sciatic nerve. In lumbar DRG we found cytoplasmic MrgC labeling mainly in small- and medium-sized neurons; coexpression with isolectin B4 (46%) and transient receptor potential vanilloid receptor 1 channel protein (TRPV1) (52%) occurred frequently, whereas calcitonin gene-related peptide (CGRP) was rarely colocalized with MrgC in DRG (11%) and dermal nerve fibers (6%). One of the MrgC agonists, BAM22, more than doubled the heat-induced cutaneous CGRP release from rat and mouse skin. The effect of BAM22, also known to activate opioid receptors, was further enhanced by combination with naloxone that had no effect on its own. This sensitizing effect proved to be independent of secondary prostaglandin formation, mast cell degranulation, protein kinase C (PKC) activation and independent of TRPV1. Nonetheless, the capsaicin-induced CGRP release was also sensitized. Receptive fields of 26 mechano-heat sensitive C-fibers were treated with MrgC agonists. Only one unit was strongly and repeatedly excited and showed a profound sensitization to heat upon BAM22+naloxone. Two other established MrgC agonists (gamma2-melanocyte stimulating hormone and BAM8-22) were ineffective. Thus, BAM22 sensitizes the capsaicin- and heat-induced CGRP release in an apparently MrgC-unrelated way. The sensitization to heat appears unusually resistant against pharmacological interventions and does not involve TRPV1.

Authors+Show Affiliations

Department of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuremberg, Universitaetsstrasse 17, D-91054 Erlangen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18065157

Citation

Hager, U A., et al. "Morphological Characterization of Rat Mas-related G-protein-coupled Receptor C and Functional Analysis of Agonists." Neuroscience, vol. 151, no. 1, 2008, pp. 242-54.
Hager UA, Hein A, Lennerz JK, et al. Morphological characterization of rat Mas-related G-protein-coupled receptor C and functional analysis of agonists. Neuroscience. 2008;151(1):242-54.
Hager, U. A., Hein, A., Lennerz, J. K., Zimmermann, K., Neuhuber, W. L., & Reeh, P. W. (2008). Morphological characterization of rat Mas-related G-protein-coupled receptor C and functional analysis of agonists. Neuroscience, 151(1), 242-54.
Hager UA, et al. Morphological Characterization of Rat Mas-related G-protein-coupled Receptor C and Functional Analysis of Agonists. Neuroscience. 2008 Jan 2;151(1):242-54. PubMed PMID: 18065157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Morphological characterization of rat Mas-related G-protein-coupled receptor C and functional analysis of agonists. AU - Hager,U A, AU - Hein,A, AU - Lennerz,J K M, AU - Zimmermann,K, AU - Neuhuber,W L, AU - Reeh,P W, Y1 - 2007/11/04/ PY - 2007/07/20/received PY - 2007/09/06/revised PY - 2007/09/24/accepted PY - 2007/12/11/pubmed PY - 2008/4/23/medline PY - 2007/12/11/entrez SP - 242 EP - 54 JF - Neuroscience JO - Neuroscience VL - 151 IS - 1 N2 - A recently described family of "orphan" receptors, called Mas-related G-protein-coupled receptors (Mrg), is preferentially expressed in small nociceptive neurons of the rodent and human dorsal root ganglia (DRG). Mrg are activated by high affinity peptide fragments derived from the proenkephalin A gene, e.g. BAM22 (bovine adrenal medullary). To study the histological distribution and functional properties of these receptors, we combined confocal immunohistochemistry in rat DRG and dermis whole mounts, using new antibodies against the rat Mas-related G-protein-coupled receptor C (MrgC), with single-fiber recordings and neurochemical experiments using isolated hind-paw skin and sciatic nerve. In lumbar DRG we found cytoplasmic MrgC labeling mainly in small- and medium-sized neurons; coexpression with isolectin B4 (46%) and transient receptor potential vanilloid receptor 1 channel protein (TRPV1) (52%) occurred frequently, whereas calcitonin gene-related peptide (CGRP) was rarely colocalized with MrgC in DRG (11%) and dermal nerve fibers (6%). One of the MrgC agonists, BAM22, more than doubled the heat-induced cutaneous CGRP release from rat and mouse skin. The effect of BAM22, also known to activate opioid receptors, was further enhanced by combination with naloxone that had no effect on its own. This sensitizing effect proved to be independent of secondary prostaglandin formation, mast cell degranulation, protein kinase C (PKC) activation and independent of TRPV1. Nonetheless, the capsaicin-induced CGRP release was also sensitized. Receptive fields of 26 mechano-heat sensitive C-fibers were treated with MrgC agonists. Only one unit was strongly and repeatedly excited and showed a profound sensitization to heat upon BAM22+naloxone. Two other established MrgC agonists (gamma2-melanocyte stimulating hormone and BAM8-22) were ineffective. Thus, BAM22 sensitizes the capsaicin- and heat-induced CGRP release in an apparently MrgC-unrelated way. The sensitization to heat appears unusually resistant against pharmacological interventions and does not involve TRPV1. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18065157/Morphological_characterization_of_rat_Mas_related_G_protein_coupled_receptor_C_and_functional_analysis_of_agonists_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)01242-0 DB - PRIME DP - Unbound Medicine ER -