Binding and Biological Activity of C-Terminally Modified Melanocortin Peptides: A Comparison Between Their Actions at Rodent MC1 and MC3 Receptors

Peng, Pei Jing; Sahm, U.G.; Doherty, Rachel Veronica Mary; Kinsman, Richard G.; Moss, S. H.; Pouton, Colin W.

doi:10.1016/s0196-9781(97)00035-1

Cited by 16 publications

(13 citation statements)

References 26 publications

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“…Furthermore, when Phe 12 was associated with Asp 10 , the affinity for MC1R of the peptide (Asp 10 , Phe 12 )-␣-MSH was reduced to 0.069% and activity to 0.009, resulting in a virtually inactive peptide. An important observation in this research was that modifications of the melanocortin peptide sequence led to analogs for which either affinity or activity, but not both, were significantly altered (Peng et al, 1997). Therefore, the data confirmed the initial observations that binding to melanocortin receptors and their activation do not depend upon the same structure (Eberle, 1988).…”

Section: Structure-activity Relationship Of Melanocortin Peptidessupporting

confidence: 81%

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Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

Catania

Gatti

Colombo

et al. 2004

Pharmacological Reviews

418

500

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Section: Structure-activity Relationship Of Melanocortin Peptidessupporting

confidence: 81%

“…C-terminally modified analogs of ␣-MSH indicated the importance of Pro 12 for binding and activity at the MC1R (Peng et al, 1997). When Pro 12 in the ␣-MSH sequence was substituted with Phe 12 , the potency of the peptide was slightly reduced.…”

Section: Structure-activity Relationship Of Melanocortin Peptidesmentioning

confidence: 99%

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

Catania

Gatti

Colombo

et al. 2004

Pharmacological Reviews

418

500

View full text Add to dashboard Cite

“…This indicates that introduction of these residues in [Nle 4 ]␣-MSH prohibited interaction with both receptors. In a previous study (32) ]␣-MSH are probably not important for a direct interaction with the receptor, since Ala substitution on positions 10 and 11 of ␣-MSH did not affect affinity on the MC3R nor the MC1R (23).…”

Section: And [D-tyr 4 ]Mt-ii On Mc4r Mc4(267-282 Mc3) Mc4(y268i)mentioning

confidence: 84%

Conformation of the Core Sequence in Melanocortin Peptides Directs Selectivity for the Melanocortin MC3 and MC4 Receptors

Oosterom

Nijenhuis

Schaaper³

et al. 1999

Journal of Biological Chemistry

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Melanocortin peptides regulate a variety of physiological processes. Five melanocortin receptors (MC-RMT-II, that also displayed lower affinity for the MC3R. This study provides a general concept for peptide receptor selectivity, in which the major determinant for a selective receptor interaction is the conformational presentation of the core sequence in related peptides to the receptor-binding pocket.

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“…Other peptides derived from POMC, including ␣MSH, ␤MSH or ACTH were inactive on rSNSR1 (Table 1). Structure-activity relationship studies revealed that the active moiety was restricted to the C-terminal part of ␥2-MSH, which has been shown to be inactive at melanocortin receptors (13). The C-terminal fragment of ␥2-MSH, namely ␥2-MSH-6-12, demonstrated full agonism and potency comparable to the full-length ␥2-MSH, with an EC 50 value of 44 Ϯ 25 nM.…”

Section: Resultsmentioning

confidence: 99%

Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats

Grazzini

Puma

Roy

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The sensory neuron-specific G protein coupled receptors (SNSRs) have been described as a family of receptors whose expression in small diameter sensory neurons in the trigeminal and dorsal root ganglia suggests an implication in nociception. To date, the physiological function(s) of SNSRs remain unknown. Hence, the aim of the present study was to determine the effects of rat SNSR1 activation on nociception in rats. The pharmacological characterization of rat SNSR1 was initially performed in vitro to identify a specific ligand, which could be used subsequently in the rat for physiological testing. Among all ligands tested, ␥2-MSH was the most potent at activating rat SNSR1. Structure-activity relationship studies revealed that the active moiety recognized by rat SNSR1 was the C-terminal part of ␥2-MSH. The radiolabeled C-terminal part of ␥2-MSH, ␥2-MSH-6 -12, bound with high affinity to membranes derived from rat skin and spinal cord, demonstrating the presence of receptor protein at both the proximal and distal terminals of dorsal root ganglia. To investigate the physiological role of SNSR, specific ligands to rat SNSR1 were tested in behavioral assays of pain sensitivity in rats. Selective rat SNSR1 agonists produced spontaneous pain behavior, enhanced heat and mechanical sensitivity when injected intradermally, and heat hypersensitivity when injected centrally, consistent with the localization of rat SNSR1 protein at central and peripheral sites. Together, these results clearly indicate that the SNSR1 plays a role in nociception and may provide novel therapeutic opportunities for analgesia. Gprotein-coupled receptors constitute one of the largest gene family of proteins that have been exploited successfully as drug targets (1). With the near completion of the human genome project, bioinformatic analyses have revealed the existence of Ϸ145 orphan receptors (1, 2). In recent years, the ''reverse pharmacology approach'' has generated Ͼ40 ligand-receptor pairings (1, 3), and the subsequent investigation of these newly discovered ligand-receptor pairings should help in understanding and elucidating their potential physiological and pathophysiological roles.We cloned a previously undescribed family of G protein-coupled receptors that we named the sensory neuron-specific receptors (SNSRs) because of their unique mRNA distribution in small nociceptive sensory neurons in dorsal root (DRG) and trigeminal ganglia (4). The SNSRs are phylogenetically related to the Mas oncogene receptor and belong to the Mas-related genes or Mrg family described for mouse and human by Dong et al. (5). Based on several analyses, this subfamily of receptors is comprised of four to six members in human (MrgX1-4 or SNSR1-6) and 32 receptors in mouse classified into three major subfamilies Mrg A, B, and C (4-7). Initially, only one SNSR gene was identified in rat (4); recently, Zylka et al. (8) have demonstrated that more than one rat SNSR͞ Mrg subtype exists. These receptors have been subclassified in a similar scheme as described for human a...

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Binding and Biological Activity of C-Terminally Modified Melanocortin Peptides: A Comparison Between Their Actions at Rodent MC1 and MC3 Receptors

Cited by 16 publications

References 26 publications

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

Conformation of the Core Sequence in Melanocortin Peptides Directs Selectivity for the Melanocortin MC3 and MC4 Receptors

Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats

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