Abstract
Based on previous studies which indicated that pituitary adenylate cyclase activating peptide (PACAP) acts as a positive inotropic and chronotropic substance in different species via the cAMP signal transduction pathway, the objective of the present work was to investigate cAMP-regulated myocardial key proteins in response to PACAP in isolated ventricular cells of the guinea pig. Surprisingly, the two molecular forms of PACAP, PACAP(1–27) and PACAP(1–38), showed no effect on intracellular cAMP-levels, L-type Ca2+ channel current or phosphorylation of troponin inhibitor (TnI) and phospholamban (PLB). Additionally, inotropy of isolated guinea-pig ventricular strips was not affected by the neuropeptide.
However, in isolated spontaneously beating guinea-pig atria, PACAP(1–27) and PACAP(1–38), but not VIP induced severe bradycardia in a dose-dependent manner. This effect could be prevented by preincubation with the PACAP receptor antagonist PACAP(6–38), by atropine and by ω-conotoxin, a blocker of neuronal N-type Ca2+channels. PACAP stimulates release of [3H]-labelled acetylcholine. Only preparations showing an increase in [3H]acetylcholine release developed bradycardia, indicating a causal relationship between both phenomena. It was concluded that PACAP exerts no influence on guinea-pig ventricular tissue, but induces negative chronotropic effects in isolated guinea-pig atria by stimulation of acetylcholine release from parasympathetic neurons via PACAP type 1 receptors.
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Seebeck, J., Schmidt, W.E., Kilbinger, H. et al. PACAP induces bradycardia in guinea-pig heart by stimulation of atrial cholinergic neurones. Naunyn-Schmiedeberg's Arch Pharmacol 354, 424–430 (1996). https://doi.org/10.1007/BF00168432
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DOI: https://doi.org/10.1007/BF00168432