Calcitonin Receptor-Like Receptor Is Expressed on Gastrointestinal Immune Cells

Hagner, Stefanie; Knauer, Jens; Haberberger, Rainer Viktor; Göke, Burkhard; Voigt, Karlheinz; McGregor, G.P.

doi:10.1159/000068365

Cited by 23 publications

(11 citation statements)

References 26 publications

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“…CGRP was found to inhibit differentiation and immunoglobulin production by pre-B cells, whereas no activity on mature B cells was reported. Intraepithelial lymphocytes from the rat gut mucosal were also found to possess specific CGRP binding sites and express the mRNA for CL (129). Physiological concentrations of CGRP inhibited pre-B cell colony formation stimulated by IL-7 (98).…”

Section: A Cgrp: Cellular Effectsmentioning

confidence: 99%

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Brain

Grant

2004

Physiological Reviews

671

542

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This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted from the pancreas. They share vasodilator activity, albeit to varying extents depending on species and tissue. In particular, CGRP has potent activity in the cerebral circulation, which is possibly relevant to the pathology of migraine, whilst vascular sources of AM contribute to dysfunction in cardiovascular disease. Both peptides exhibit potent activity in microvascular beds. All three peptides can act on a family of CGRP receptors that consist of calcitonin receptor-like receptor (CL) linked to one of three receptor activity-modifying proteins (RAMPs) that are essential for functional activity. The association of CL with RAMP1 produces a CGRP receptor, with RAMP2 an AM receptor and with RAMP3 a CGRP/AM receptor. Evidence for the selective activity of the first nonpeptide CGRP antagonist BIBN4096BS for the CGRP receptor is presented. The cardiovascular activity of these peptides in a range of species and in human clinical conditions is detailed, and potential therapeutic applications based on use of antagonists and gene targeting of agonists are discussed.

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Section: A Cgrp: Cellular Effectsmentioning

confidence: 99%

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Brain

Grant

2004

Physiological Reviews

671

542

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“…This contrasts with our finding of unchanged serum SP and CGRP (Figure 4E-F) and suggests the NK1 upregulation and aberrant SP-mediated signaling observed in this study do not arise from increased whole-body SP. In contrast to SP, CGRP is anti-inflammatory in many tissues 50,51 and participates in immune responses by decreasing the release of proinflammatory cytokines from multiple cell types 52,53 . In patients with IBD, CGRP is decreased in the intestinal mucosa, and the magnitude of this decrease is correlated with the severity of IBD symptoms 54 .…”

Section: Discussionmentioning

confidence: 99%

Altered substance P signaling underlies perivascular sensory nerve dysfunction in inflammatory bowel disease

Norton

Grunz-Borgmann

Hart

et al. 2020

Preprint

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Objective: Inflammatory Bowel Disease (IBD) is associated with cardiovascular disease risk and impaired intestinal blood flow, but the functional role of perivascular nerves that control vasomotor function of mesenteric arteries (MAs) perfusing the intestine is unknown in IBD. Because perivascular sensory nerves and their transmitters calcitonin gene-related peptide (CGRP) and substance P (SP) are important mediators of both vasodilation and inflammatory responses, our objective was to identify IBD-related deficits in perivascular sensory nerve function and vascular neurotransmitter signaling.Approach and Results: In MAs from an IL-10 -/mouse model, we found that IBD significantly impairs EFS-mediated sensory vasodilation and sensory inhibition of sympathetic vasoconstriction, despite decreased sympathetic nerve density and vasoconstriction. The MA content and EFS-mediated release of both CGRP and SP are slightly decreased with IBD, but IBD has different effects on each transmitter. CGRP nerve density, receptor expression, hyperpolarization and vasodilation are preserved with IBD. In contrast, SP nerve density and receptor expression are increased, and SP hyperpolarization and vasodilation are impaired with IBD. A critical finding is that blocking neurokinin 1 (SP) receptors restored EFS-mediated sensory vasodilation and enhanced CGRP-mediated vasodilation in MAs from IBD but not Control mice.Conclusions: An aberrant role for the perivascular sensory neurotransmitter SP and its downstream signaling in MAs underlies vascular dysfunction with IBD. With IBD, SP signaling impedes CGRP-mediated sensory vasodilation, contributing to impaired blood flow. Substance P and NK1 receptors may represent an important target for treating vascular dysfunction in IBD.

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“…Polymerase chain reaction (PCR) experiments were carried out as described previously. 8 The primers used were as follows: Negative controls were included either by omitting reverse transcriptase from cDNA synthesis or by omitting cDNA from the PCR amplifications.…”

Section: Human Tissuesmentioning

confidence: 99%