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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nyborg, N. C. Sheykhzade, M. |
| Description | Author Affiliation: Sheykhzade M ( Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen O.) |
| Abstract | 1. In this study we characterized the CGRP-receptor subtype by Schild-plot analysis using the C-terminal fragment, human-alphaCGRP(8-37), a putative competitive CGRP1-receptor selective antagonist. In addition, the effect of rat-alphaCGRP was compared with that of homologous peptides rat-betaCGRP, rat-amylin, rat-adrenomedullin and [Cys(Acm)2,7]-human-alphaCGRP, a putative selective CGRP2-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(-5) M prostaglandin F2alpha (PGF2alpha), after which agonists were added to the organ bath in a cumulative manner. 3. Rat-alphaCGRP induced endothelium-independent relaxations in male and female Sprague-Dawley rats. Rat-betaCGRP concentration-response relations (10[-11]-10[-7] M) were similar to those of rat-alphaCGRP in either sex. The maximal relaxations induced by rat-amylin and rat-adrenomedullin, both at 10(-6) M, were significantly (P<0.05) lower than those induced by rat-alpha- and rat-betaCGRP. In contrast, the selective CGRP2-receptor agonist [Cys(Acm)2,7]-human-alphaCGRP failed to induce significant relaxations at the highest concentration used (10[-7] M) in the coronary arteries of male and female rats. 4. The C-terminal fragment, human-alphaCGRP(8-37) blocked concentration-dependently (10[-7]-10[-6] M) the rat-alphaCGRP-induced relaxation in 10(-5) M PGF2alpha-precontracted coronary arteries. The slopes of the regression lines of the Schild-plots for both male and female rats were not significantly (P>0.05) different from unity and the pA2 values for human-alphaCGRP(8-37) were 6.93 and 6.98 in arteries from male and female rats, respectively. There was no significant (P>0.05) difference in estimated pKB values for human-alphaCGRP(8-37) between male (6.99+/-0.10, n=13) and female (6.95+/-0.08, n=13) rats. 5. The concentration-response relationships for rat-alpha- and rat-betaCGRP were similar in male and female Sprague Dawley rats. The predominant CGRP receptor subtype in small intramural coronary arteries appeared to belong to the CGRP1-receptor subtype in both sexes. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 123 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1998-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Arteries Metabolism Coronary Vessels Receptors, Calcitonin Gene-Related Peptide Adrenomedullin Amyloid Pharmacology Animals Drug Effects Calcitonin Gene-Related Peptide Analogs & Derivatives Endothelium, Vascular Islet Amyloid Polypeptide Peptides Rats, Sprague-Dawley Agonists Antagonists & Inhibitors Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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