Positive inotropy of calcitonin gene-related peptide and amylin on porcine isolated myocardium.
Isolated porcine myocardial trabeculae from right atria and left ventricles were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Alpha calcitonin gene-related peptide (alpha-CGRP) increased contractile force in nearly half of the trabeculae, whereas the selective CGRP(2) receptor agonist [Cys(acetylmethoxy)(2,7)]-CGRP had effect in only a few. Preincubation with the CGRP(1) receptor antagonist alpha-CGRP-(8-37) (10(-6) M) almost completely blocked positive inotropic responses to alpha-CGRP. Amylin had weak positive inotropic effects in some atrial, but not in ventricular trabeculae. Adrenomedullin did not affect contractility in either atrial or ventricular trabeculae. In conclusion, these results suggest that alpha-CGRP has a positive inotropic effect that can be mediated by both CGRP(1) and CGRP(2) receptors. Amylin seems to have a potential positive inotropic effect on atrial tissue, whereas no direct effect of adrenomedullin could be measured.
Saetrum Opgaard
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Department of Pharmacology, Erasmus University, 3000 DR, Rotterdam, The Netherlands. osaetrum@uci.edu
de Vries
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Tom
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B
Edvinsson
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Saxena
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PR
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000819:agonists; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016276:Ventricular Function
D000682:Amyloid; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; D014662:Vasoconstrictor Agents; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine