Arachidonic acid and bradykinin share a common pathway to release neuropeptide from capsaicin-sensitive sensory nerve fibers of the guinea pig heart.
The ability of arachidonic acid (AA) and bradykinin to release calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from capsaicin-sensitive primary afferents was studied in guinea pig isolated and perfused heart. Infusion of AA (50 microM to 5 mM, 0.5 ml/min over 2 min) produced a remarkable and dose-dependent CGRP-LI release that was abolished by in vitro capsaicin (10 microM) pretreatment or in the presence of indomethacin (10 microM). The capsaicin antagonist ruthenium red (10 microM) did not affect the CGRP-LI release produced by AA, whereas it blocked that produced by capsaicin (10 microM). In vitro capsaicin pretreatment reduced the increase in heart rate evoked by AA, whereas it did not affect the increase in coronary flow and decrease in contractility. Bradykinin (10 microM, 0.5 ml/min over 2 min) induced CGRP-LI release in a similar manner to that produced by AA, with the only difference being that in the presence of indomethacin, a residual increase in CGRP-LI outflow was still observed. AA increased the outflow of 6-keto-prostaglandin (PG) F1 alpha, PGE2 and leukotriene B4, whereas bradykinin enhanced only the release of 6-keto-PGF1 alpha. Infusion of either PGI2 or PGE2 (1-100 microM) released CGRP-LI in a dose-dependent manner and with a similar potency. PGI2 (100 microM)- or PGE2 (100 microM, 0.5 ml/min over 2 min)-evoked release was abolished by previous exposure to capsaicin and not affected by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
Geppetti
P
P
Institute of Internal Medicine IV, University of Florence, Italy.
Del Bianco
E
E
Tramontana
M
M
Vigano
T
T
Folco
G C
GC
Maggi
C A
CA
Manzini
S
S
Fanciullacci
M
M
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion
D015777:Eicosanoids; D016718:Arachidonic Acid; D011464:Epoprostenol; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D002211:Capsaicin; D001920:Bradykinin