Positive inotropy mediated via CGRP receptors in isolated human myocardial trabeculae

• Published in: European journal of pharmacology 2000-06, Vol.397 (2), p.373-382
• Main Authors: Saetrum Opgaard, Ole, Hasbak, Philip, de Vries, René, Saxena, Pramod R, Edvinsson, Lars
• Format: Article
• Language: English
• Subjects: Adrenomedullin; Amylin; Amyloid - pharmacology; Atrial Function; Biological and medical sciences; Calcitonin gene-related peptide (CGRP); Calcitonin Gene-Related Peptide - pharmacology; Calcitonin receptor-like receptor; Cardiotonic Agents - pharmacology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Heart; Heart - drug effects; Heart - physiology; Heart Atria - drug effects; Heart Atria - metabolism; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Humans; In Vitro Techniques; Islet Amyloid Polypeptide; Myocardial contraction; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Norepinephrine - pharmacology; Peptides - pharmacology; Receptor associated modifying protein (RAMP); Receptors, Calcitonin Gene-Related Peptide - agonists; Receptors, Calcitonin Gene-Related Peptide - genetics; Receptors, Calcitonin Gene-Related Peptide - physiology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Ventricular Function; Vertebrates: cardiovascular system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00233-8

Isometric contractile force were studied on isolated human myocardial trabeculae that were paced at 1.0 Hz in tissue baths. Alpha calcitonin gene-related peptide (α-CGRP) had a potent positive inotropic effect in most trabeculae from both the right atrium and left ventricle, and this effect was partially antagonized by the CGRP 1 receptor antagonist α-CGRP-(8-37) (10 −6 M). Amylin and the CGRP 2 receptor agonist [Cys(acetylmethoxy) 2,7]CGRP had a positive inotropic effect in some trabeculae, whereas adrenomedullin had no inotropic effect. Using reverse transcriptase–polymerase chain reaction (PCR) mRNAs encoding the human calcitonin receptor-like receptor and the receptor associated modifying proteins (RAMPs) RAMP1, RAMP2, and RAMP3 were detected in human myocardial trabeculae from both the right atrium and left ventricle. In conclusion, functional CGRP 1 and CGRP 2 receptors may mediate a positive inotropic effect at both the atrial and ventricular level of the human heart. mRNAs for calcitonin receptor-like receptor and specific RAMPs further support the presence of CGRP receptors.