Positive inotropy mediated via CGRP receptors in isolated human myocardial trabeculae.
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 (alpha-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 alpha-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.
Saetrum Opgaard
O
O
Department of Pharmacology, Erasmus University, 3000 DR, Rotterdam, Netherlands. osaetrum@uci.edu
Hasbak
P
P
de Vries
R
R
Saxena
P R
PR
Edvinsson
L
L
D053607:Adrenomedullin; D000682:Amyloid / Q000494:pharmacology; D016275:Atrial Function; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D016276:Ventricular Function
D000682:Amyloid; D002316:Cardiotonic Agents; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D012333:RNA, Messenger; D018015:Receptors, Calcitonin Gene-Related Peptide; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine