Positive inotropic effects of CGRP and isoprenaline: analogies and differences.
In guinea-pig isolated left atria, electrically stimulated at 1 Hz, isoprenaline and calcitonin gene-related peptide (CGRP) induced a positive inotropic effect in the same concentration range (0.3-100 nM). The increase in contractile tension induced by both agonists was associated with a reduction in time to peak tension and relaxation time. However CGRP was more active than isoprenaline in reducing the time to peak; this effect was more evident when the bath temperature was reduced from 30 degrees to 24 degrees C. The positive inotropic effects of isoprenaline and CGRP were potentiated by forskolin (30 nM), a direct activator of adenylcyclase; on the other hand, cholera toxin (1 microgram/ml), which irreversibly ribosylates Gs protein, did not modify the effect of CGRP, while antagonizing the concentration-response curve for isoprenaline. It is concluded that the increase in atrial contractile tension produced by isoprenaline and CGRP are linked to the adenylcyclase system in a different manner.
Mantelli
L
L
Department of Pharmacology, University of Florence, Italy.
Amerini
S
S
Filippi
S
S
Ledda
F
F
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male
D002316:Cardiotonic Agents; D005576:Colforsin; D002772:Cholera Toxin; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol