Prostaglandins and CGRP release from cardiac sensory nerves.
(1) The possible influence of prostaglandins (PG) E1 and I2 as well as ischaemia, ouabain and bradykinin on the outflow of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI) from the guinea-pig heart was studied in vitro. (2) Exposure to PGE1 (10(-5) M), but not PGI2 (10(-5) M), induced an increased outflow, suggesting release of CGRP-LI. PGE1 simultaneously increased the contractile force and heart rate while no effects were observed on perfusate volume or outflow of NPY-LI. PGI2 had no effect on contractile parameters or coronary flow. In separate experiments on capsaicin-pretreated animals, the stimulatory effects of PGE1 on heart rate and contractile force remained unchanged while no increased CGRP-LI outflow was detectable. (3) Ouabain, bradykinin and reperfusion after total stop-flow ischaemia was associated with an indomethacin-resistant increase in perfusate levels of CGRP-LI but not of NPY-LI. While ouabain markedly increased the contractile force, exposure to bradykinin or ischaemia did not induce any clear-cut changes in contractile force or heart rate. (4) Capsaicin-exposure evoked a markedly increased outflow of CGRP-LI but not of NPY-LI in combination with an increase in heart rate and a decrease in contractile force. Repeated administration of capsaicin induced tachyphylaxis. The stimulatory effects of capsaicin on CGRP-LI outflow and heart rate, but not the negative inotropic effect, did not occur in capsaicin-pretreated animals. (5) It is concluded that PGE1, but not PGI2, can activate cardiac capsaicin-sensitive fibres as revealed by increased outflow of CGRP-LI.(ABSTRACT TRUNCATED AT 250 WORDS)
Franco-Cereceda
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Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D003327:Coronary Disease / Q000503:physiopathology; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism
D009478:Neuropeptide Y; D011453:Prostaglandins; D010042:Ouabain; D011464:Epoprostenol; D000527:Alprostadil; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin