Effects of colchicine on the development of tachyphylaxis to calcitonin gene-related peptide in the guinea pig heart.
Calcitonin gene-related peptide (CGRP) induced a concentration-dependent positive inotropic and chronotropic effect on the spontaneously beating right atrium subject to tachyphylaxis upon extended incubation. This stimulatory effect was mimicked by capsaicin. After incubation with colchicine there was a marked attenuation of the decline in the prolonged response to CGRP or capsaicin and no development of CGRP tachyphylaxis. Colchicine incubation did not influence the capsaicin-induced stimulation of the frequency or CGRP outflow in whole heart preparations. Thus, the present data suggest that the development of CGRP tachyphylaxis is a specific receptor-mediated event which can be inhibited by colchicine, probably by disruption of membrane bound proteins.
Franco-Cereceda
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Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
D000818:Animals; D016275:Atrial Function; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D013618:Tachyphylaxis
D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D003078:Colchicine; D009638:Norepinephrine