Differential vasodilator profile of calcitonin gene-related peptide in porcine large and smail diameter coronary artery rings

Foulkes, Roly; Shaw, Nina; Bose, Chris; Hughes, Bernadette

doi:10.1016/0014-2999(91)90337-p

Cited by 36 publications

(16 citation statements)

References 19 publications

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“…Another study showed that human‐αCGRP(8–37) has competitive antagonistic activity in pig coronary arteries with a p K B value of 6.7 (Gray et al , 1991). In rat mesenteric small artery, the p K B value falls within the range 7.2 to 7.6 (Foulkes et al , 1991; Lei et al , 1994; Nuki et al , 1994). In rat thoracic aorta, human‐αCGRP(8–37) seems to be a non‐competitive antagonist of human‐αCGRP (Gray et al , 1991) adding to the complexity of CGRP‐receptor characterization.…”

Section: Discussionmentioning

confidence: 97%

“…Experimental procedures can also affect estimation of affinity data for human‐αCGRP. Foulkes et al (1991) found that the affinity of small diameter pig coronary artery to human‐αCGRP(8–37) was markedly altered by the experimental protocol. The pA 2 value for human‐αCGRP(8–37) was around 7.02 when the vessel exposure to human‐αCGRP(8–37) was minimized by using one concentration of human‐αCGRP(8–37) per preparation, while it increased to 8.67 as the exposure time to human‐αCGRP(8–37) was extended when three different increasing antagonist concentrations were used per vessel.…”

Section: Discussionmentioning

confidence: 99%

“…The p K B ‐values for human‐αCGRP(8–37) which is accepted as a CGRP 1 ‐receptor antagonist, cover a considerable range from about 6 to 8.5 in the rat (see review by Poyner, 1995). In large diameter pig coronary artery a p K B value has been estimated of 5.7, whereas that for small diameter pig coronary artery was close to 7.0 (Foulkes et al , 1991). Another study showed that human‐αCGRP(8–37) has competitive antagonistic activity in pig coronary arteries with a p K B value of 6.7 (Gray et al , 1991).…”

Section: Discussionmentioning

confidence: 99%

“…The pA 2 value for human‐αCGRP(8–37) was around 7.02 when the vessel exposure to human‐αCGRP(8–37) was minimized by using one concentration of human‐αCGRP(8–37) per preparation, while it increased to 8.67 as the exposure time to human‐αCGRP(8–37) was extended when three different increasing antagonist concentrations were used per vessel. The slope of the Schild‐plot was also influenced by the exposure time, being markedly flatter (slope = 0.67) compared to that under minimized exposure conditions (slope = 0.84) (Foulkes et al , 1991). Foulkes et al (1991) also showed that administration of human‐αCGRP(8–37) itself to porcine coronary arteries precontracted with acetylcholine, elicited a further contraction in a third of the preparations.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of calcitonin gene‐related peptide(CGRP) receptors in intramural coronary arteries from male and female Sprague Dawley rats

Sheykhzade

Nyborg

1998

British J Pharmacology

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1 In this study we characterized the CGRP-receptor subtype by Schild-plot analysis using the Cterminal fragment, human-aCGRP(8 ± 37), a putative competitive CGRP 1 -receptor selective antagonist. In addition, the e ect of rat-aCGRP was compared with that of homologous peptides rat-bCGRP, ratamylin, rat-adrenomedullin and [Cys(Acm) 2,7 ]-human-aCGRP, a putative selective CGRP 2 -receptor agonist, in the left coronary arteries of 3 months old male and female Sprague Dawley rats. 2 Isolated rings from the distal, intramural part of the left anterior descending (LAD) coronary artery in both groups of rats were mounted on a double wire-myograph. The arteries were then stretched to their optimal lumen diameter for active tension development and precontracted with 10 75 M prostaglandin F 2a (PGF 2a ), after which agonists were added to the organ bath in a cumulative manner. 3 Rat-aCGRP induced endothelium-independent relaxations in male and female Sprague-Dawley rats. Rat-bCGRP concentration-response relations (10 711 ± 10 77 M) were similar to those of rat-aCGRP in either sex. The maximal relaxations induced by rat-amylin and rat-adrenomedullin, both at 10 76 M, were signi®cantly (P50.05) lower than those induced by rat-a-and rat-bCGRP. In contrast, the selective CGRP 2 -receptor agonist [Cys(Acm) 2,7 ]-human-aCGRP failed to induce signi®cant relaxations at the highest concentration used (10 77 M) in the coronary arteries of male and female rats. 5 The C-terminal fragment, human-aCGRP(8 ± 37) blocked concentration-dependently (10 77 ± 10 76 M) the rat-aCGRP-induced relaxation in 10 75 M PGF 2a -precontracted coronary arteries. The slopes of the regression lines of the Schild-plots for both male and female rats were not signi®cantly (P40.05) di erent from unity and the pA 2 values for human-aCGRP(8 ± 37) were 6.93 and 6.98 in arteries from male and female rats, respectively. There was no signi®cant (P40.05) di erence in estimated pK B values for human-aCGRP(8 ± 37) between male (6.99+0.10, n=13) and female (6.95+0.08, n=13) rats. 6 The concentration-response relationships for rat-a-and rat-bCGRP were similar in male and female Sprague Dawley rats. The predominant CGRP receptor subtype in small intramural coronary arteries appeared to belong to the CGRP 1 -receptor subtype in both sexes.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of calcitonin gene‐related peptide(CGRP) receptors in intramural coronary arteries from male and female Sprague Dawley rats

Sheykhzade

Nyborg

1998

British J Pharmacology

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“…CGRP immunoreactivity has been shown to be widely distributed in neural tissue and coexists with substance P in the cardiovascular system [2][3][4], It has a potent dilator action on human coronary arter Regional variations in CGRP vasodilator activity and CGRP tachyphylaxis have been shown in porcine and human coronary vessels [11], The distribution of CGRPbinding sites and receptor subtypes has been shown to exhibit species variability as well as regional variations in different vascular beds [12,13], It is unclear whether CGRP receptors are altered in diseases, such as ischaemic heart disease. To elucidate the effect of tissue pathology, we have examined the response of isolated segments of healthy and atheromatous human coronary arteries to CGRP, in combination with autora diographic techniques to establish the distribution and characteristics of binding sites for this peptide.…”

Section: Introductionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide in Healthy and Atheromatous Human Epicardial Coronary Arteries

Luu

Dashwood²,

Chester³

et al. 1995

J Vasc Res

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To examine the possible role of calcitonin gene-related peptide (CGRP) in the control of human coronary vascular tone, we have investigated the action of this peptide in healthy and atheromatous human epicardial coronary arteries and localised [¹²⁵I]CGRP-binding sites in these vessels. Isolated arteries were obtained from 10 cardiomyopathic patients and 6 patients with ischaemic heart disease (IHD), who were undergoing heart transplantation. CGRP elicited concentration-dependent vasodilatation in preconstricted vessels. Both healthy and diseased coronary arteries exhibited similar maximum responses and sensitivity to this peptide. Removal of the endothelium did not diminish the vasodilator action of CGRP in non-atherosclerotic coronary arteries. [¹²⁵I]CGRP bound to tissue sections in a concentration-dependent manner. Binding was similar in healthy and atheromatous vessels, with a B_max value of 10.2 ± 5.6 and 18.9 ± 3.0 amol/mg protein, and dissociation constant (K_d) of 0.07 ± 0.1 and 0.18 ± 0.1 nM, respectively. Dense [¹²⁵I]CGRP binding was mainly associated with vascular smooth muscle cells of both normal and diseased vessels with some patches of binding to regions of atherosclerotic plaque in vessels from patients with IHD. These data indicate that CGRP is a potent endothelium-independent vasodilator in the human coronary vasculature. The preservation of dilator function and CGRP receptor binding in atherosclerotic coronary arteries suggests that this peptide may play a role in the control or maintenance of vascular tone in certain disease states.

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Functional and Molecular Characterization of Receptor Subtypes Mediating Coronary Microvascular Dilation to Adenosine

Hein

Wang

Zoghi

et al. 2001

Journal of Molecular and Cellular Cardiology

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Differential vasodilator profile of calcitonin gene-related peptide in porcine large and smail diameter coronary artery rings

Cited by 36 publications

References 19 publications

Characterization of calcitonin gene‐related peptide(CGRP) receptors in intramural coronary arteries from male and female Sprague Dawley rats

Characterization of calcitonin gene‐related peptide(CGRP) receptors in intramural coronary arteries from male and female Sprague Dawley rats

Calcitonin Gene-Related Peptide in Healthy and Atheromatous Human Epicardial Coronary Arteries

Functional and Molecular Characterization of Receptor Subtypes Mediating Coronary Microvascular Dilation to Adenosine

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