Circadian Profile of Plasma Calcitonin Gene-Related Peptide in Healthy Man*

Abstract

Calcitonin gene-related peptide (CGRP) is known to exert potent cardiovascular effects and is presumed to participate in the neural control of circulation and blood flow. It has been assayed in many physiological and disease conditions, yet virtually nothing is known of the normal fluctuations in its circulating levels. We have studied the variability throughout a 24-h period of plasma concentrations of CGRP in eight recumbent healthy volunteers (four men and four women, 25-37 yr old), after careful standardization of their daily diet and routine schedules. A correlation with the circadian rhythms of blood pressure (BP), heart rate (HR), and plasma aldosterone (PA), PRA, plasma cortisol (PC), and atrial natriuretic peptide (ANP) was also made. Plasma CGRP concentrations ranged from a mean peak value of 18.1 +/- 1.5 pmol/L to a mean lowest value of 11.7 +/- 0.4 pmol/L (P less than 0.05). The mean circadian acrophase of CGRP (calculated by cosinor analysis to occur at 2314 h) anticipated the corresponding acrophases of the other hormones (0122, 0528, 0809, and 0840 h for ANP, PRA, PA, and PC, respectively). Instead, BP and HR rhythms seemed to be antiphasic with the ANP rhythm (calculated acrophases occurred at 1356, 1339, and 1314 h for systolic BP, diastolic BP, and HR, respectively). Our data demonstrate that, like many other hormones, CGRP circulates in plasma with a circadian rhythm. There seems to be a temporal sequence starting with the nocturnal rise in plasma CGRP concentrations and progressing with the ensuing elevations of ANP, PRA, PA, and PC, whereas BP and HR are kept to their lowest values. These findings are in favor of a physiological role of CGRP in the complex regulation of BP homeostasis.

Evidence for the Presence of Molecules Related to the Neuropeptide CGRP in Two Cephalopods, <i>Sepia officinalis </i>and <i>Nautilus macromphalus</i>: Comparison with Its Target Organ Distribution

“…This level of CGRP in cephalopods are in the same range as the plasma levels measured in the teleost, Anguilla anguilla [18]. They are much higher than in mammals, in which CGRP is considered to act via local controls [50]. The hemolymph CGRP level is coherent with the affinity constant of the cephalopod CGRP-like receptor, as calculated by the Scatchard parameters in the target tissues.…”

Adrenomedullin 2 Enhances Beiging in White Adipose Tissue Directly in an Adipocyte-autonomous Manner and Indirectly through Activation of M2 Macrophages

“…Both adipocyte metabolism and thermogenesis are under the control of circadian rhythms (42,43). CGRP, another member of the same peptide family as ADM2, has been found to have a circadian profile of plasma concentration (44). Thus it is possible that ADM2 could function in a circadian manner to regulate beiging and metabolic thermogenesis.…”

Hormonal replacement therapy affects calcitonin gene-related peptide and atrial natriuretic peptide secretion in postmenopausal women

“…Bound and free ANP were separated by the addition of 1 ml precipitating reagent (horse anti-sheep immunoglobulin serum), incubated for 30 min at room temperature, centrifuged for 30 min at 2000 g, and the precipitate was counted in a g-counter. The intra-assay and interassay coefficients of variation were 8.6 and 11.6% respectively and the sensitivity was 2.3 pg/ml (20).…”

“…There was no interference with the assay from human calcitonin, human amylin, rat amylin amide and substance P. The cross-reactivity of the antiserum is, on a molar basis, 100% with hCGRP, hCGRP II, rat CGRP and rat CGRP II. Recovery was assessed using increasing amounts of standard hCGRP, and an 85% recovery was found (20).…”