Characterization of receptors for calcitonin gene‐related peptide and adrenomedullin on the guinea‐pig vas deferens

Poyner, David R.; Taylor, Gillian; Tomlinson, A. Elaine; Richardson, Alan G; Smith, David M.

doi:10.1038/sj.bjp.0702437

Cited by 44 publications

(18 citation statements)

References 32 publications

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“…In studies with ARA in the soleus, no inverse agonism at concentrations up to 1 mM were seen [37]. Selectivity of ARA over other amylin-related peptides as an amylin antagonist has been demonstrated in the rat skeletal muscle [38] and in guinea pig vas deferens [39]. Efficacy of ARA to antagonize metabolic effects of amylin has been demonstrated in vivo in rats [40], but no direct comparisons against other amylin-related peptides have been reported.…”

Section: Methodsmentioning

confidence: 95%

Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity

Mather

Paradisi

Leaming

et al. 2002

Diabetes Metabolism Res

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Section: Methodsmentioning

confidence: 95%

Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity

Mather

Paradisi

Leaming

et al. 2002

Diabetes Metabolism Res

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“…However, the results of these differential-affinity studies have been inconsistent [15,16], and a recent report by Rorabaugh et al [17] questioned the existence of separate CGRP2 receptors. Recent molecular data suggest that CGRP receptors use accessory proteins to form functional receptor complexes and that receptor diversity is increased by the combinatorial use of transmembrane receptors and receptor-associated proteins.…”

Section: Introductionmentioning

confidence: 97%

Female Sex Steroid Hormones and Pregnancy Regulate Receptors for Calcitonin Gene-Related Peptide in Rat Mesenteric Arteries, but Not in Aorta1

Yallampalli¹,

Kondapaka²,

Lanlua³

et al. 2004

Biology of Reproduction

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Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide known to be involved in the regulation of vascular tone. Results of previous studies from our laboratory and others suggest that vascular sensitivity to CGRP is enhanced during pregnancy and that the female sex steroid hormones estradiol-17beta (E2) and progesterone (P4) may be involved in this process. We hypothesized that CGRP receptors in the mesenteric artery are increased during pregnancy and with sex steroid hormone treatments. In the present study, we investigated whether pregnancy and female sex steroid hormones modulate the CGRP-receptors CGRP-A and CGRP-B in the mesenteric artery in the rat. The CGRP-A receptor consists of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1); however, the CGRP-B receptor needs to be further characterized. Messenger RNA levels for CRLR and RAMP1 were assessed by reverse transcription-polymerase chain reaction, and CGRP-B receptor proteins levels were determined by Western blot analysis. In addition, [125I]CGRP binding was measured by Scatchard analysis. Both mRNA for CGRP-A (CRLR and RAMP1) and the protein for CGRP-B receptors in mesenteric arteries were increased with pregnancy compared to nonpregnant, diestrous animals. A P4 antagonist, RU-486, downregulated and P4 upregulated these receptors in mesenteric arteries (P < 0.05) in pregnant rats. In adult ovariectomized rats, P4 upregulated CRLR and RAMP1 mRNA levels as well as [125I]CGRP-binding sites. The CGRP-B-receptor protein levels were significantly (P < 0.05) elevated by P4 and by combined E2 and P4 treatment. Together with earlier findings, these data suggest that increases in the expression of CGRP-A (CRLR and RAMP1) and CGRP-B receptors in mesenteric arteries may be important in reducing vascular resistance and in vascular adaptations that occur during pregnancy; in addition, P4 may be involved in this process.

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“…However, these differential affinity studies have been inconsistent [17,18], and a recent report by Rorabaugh et al [19] questioned the existence of separate CGRP2 receptors. Recent studies from our laboratory showed the existence of a CGRP receptor that is different from a well-characterized CGRP receptor component, calcitonin receptor-like receptor (CRLR) [20,21].…”

Section: Introductionmentioning

confidence: 98%

Mechanisms Involved in Calcitonin Gene-Related Peptide-Induced Relaxation in Pregnant Rat Uterine Artery1

Gangula¹,

Thota²,

Wimalawansa³

et al. 2003

Biology of Reproduction

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Human and rodent studies have demonstrated that calcitonin gene-related peptide (CGRP), a potent vasodilator, relaxes uterine tissue during pregnancy but not during labor. The vascular sensitivity to CGRP is enhanced during pregnancy, compared to nonpregnant human uterine arteries. In the present study, we hypothesized that uterine artery relaxation effects of CGRP are enhanced in pregnant rats compared to nonpregnant diestrus rats (NP-DE) and that several secondary messenger systems are involved in this process. We also hypothesized that the expression of CGRP-A receptor components, calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1), and CGRP-B receptors are greater in pregnant rats. For vascular relaxation studies, uterine arteries from either NP-DE or Day 18 pregnant rats were isolated, and responsiveness of the vessels to CGRP was examined with a small vessel myograph. CGRP-A and CGRP-B receptor expressions were assessed by RT-PCR and Western immunoblotting, respectively. CGRP (10(-10)--10(-7) M) produced a concentration-dependent relaxation of norepinephrine-induced contractions in both NP-DE and Day 18 pregnant rat uterine arteries. Pregnancy increased the vasodilator sensitivity to CGRP significantly (P < 0.05) compared to NP-DE rats. CGRP receptor antagonist, CGRP8-37, inhibited CGRP-induced relaxation of pregnant uterine arteries. The CGRP-induced relaxation was not affected by NG-nitro-l-arginine methyl ester (L-NAME) (nitric oxide inhibitor, 10(-4) M) but was significantly (P < 0.05) attenuated by inhibitors of guanylate cyclase (ODQ, 10(-5) M) and adenylate cyclase (SQ 22536, 10(-5) M). CGRP-induced vasorelaxation was significantly (P < 0.05) attenuated by potassium channel blockers KATP (glybenclamide, 10(-5) M) and K(CA) (tetraethylammonium, 10(-3) M). The expression of CRLR and RAMP1 was significantly (P < 0.05) elevated during pregnancy compared to nonpregnant diestrus state (NP-DE). However, CGRP-B receptor proteins in uterine arteries were not altered with pregnancy compared to those of NP-DE. These studies suggest that CGRP-induced increases in uterine artery relaxation may play a role in regulating blood flow to the uterus during pregnancy and, therefore, in fetal growth and survival.

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Characterization of receptors for calcitonin gene‐related peptide and adrenomedullin on the guinea‐pig vas deferens

Cited by 44 publications

References 32 publications

Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity

Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity

Female Sex Steroid Hormones and Pregnancy Regulate Receptors for Calcitonin Gene-Related Peptide in Rat Mesenteric Arteries, but Not in Aorta1

Mechanisms Involved in Calcitonin Gene-Related Peptide-Induced Relaxation in Pregnant Rat Uterine Artery1

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