Differential release of calcitonin gene-related peptide and neuropeptide Y from the isolated heart by capsaicin, ischaemia, nicotine, bradykinin and ouabain.
The influence of various drugs as well as total ischaemia on the outflow of calcitonin gene-related peptide (CGRP), which is present in sensory nerves, and neuropeptide Y (NPY), which is co-stored with noradrenaline (NA), from the isolated guinea-pig heart, was studied in vitro. Capsaicin exposure and total ischaemia for 5-30 min induced a Ca2+-dependent increase in the outflow, suggesting release, of CGRP- but not NPY-like immunoreactivity (LI) from the heart. When characterized by high performance liquid chromatography (HPLC), the CGRP-LI present in heart extracts and the released CGRP-LI by capsaicin eluted in a major peak corresponding to synthetic CGRP. Incubation with morphine, indomethacin or reserpine pretreatment did not influence the capsaicin-evoked release of CGRP-LI. Capsaicin pretreatment depleted the cardiac content of CGRP-LI but not NPY-LI. The increase in perfusate volume observed after 30 min ischaemia in controls was reduced after capsaicin pretreatment. Nicotine exposure induced release of CGRP- as well as NPY-LI in a concentration- and Ca2+-dependent manner. The increased outflow of NPY-LI was not influenced by capsaicin pretreatment. Among other agents tested, bradykinin and ouabain caused increased outflow of CGRP but not of NPY-LI. Noradrenaline, tyramine, histamine, vasopressin, alpha,beta methylene ATP, ATP or adenosine induced changes in cardiac contractility or flow but did not evoke any detectable release of CGRP- or NPY-LI. In conclusion, the release of multiple neuropeptides can be studied in combination with contractile recordings using the isolated perfused guinea-pig whole heart preparation. Activation of cardiac sensory nerves by capsaicin, nicotine, bradykinin and ouabain, as well as ischaemia, induced release of CGRP while nicotine also evoked NPY release.
Franco-Cereceda
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Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Saria
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Lundberg
J M
JM
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007511:Ischemia / Q000503:physiopathology; D009478:Neuropeptide Y / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000187:drug effects
D009478:Neuropeptide Y; D009479:Neuropeptides; D010042:Ouabain; D009538:Nicotine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin