PACAP-38 activates parasympathetic nerves in isolated, blood-perfused dog atria

• Published in: European journal of pharmacology 1996-11, Vol.315 (3), p.289-296
• Main Authors: Yonezawa, Takanori, Furukawa, Yasuyuki, Lakhe, Manoj, Nagashima, Yoshito, Hirose, Masamichi, Chiba, Shigetoshi
• Format: Article
• Language: English
• Subjects: Acetylcholine; Animals; Biological and medical sciences; Cardiovascular system; Chronotropism; Dog; Dogs; Dose-Response Relationship, Drug; Heart; Heart Atria - drug effects; Inotropism; Medical sciences; Miscellaneous; Neuropeptides - pharmacology; Neuroprotective Agents - pharmacology; PACAP-(6–38) (pituitary adenylate cyclase-activating polypeptide-(6–38)); PACAP-38 (pituitary adenylate cyclase-activating polypeptide-38); Parasympathetic nervous system; Parasympathetic Nervous System - drug effects; Pharmacology. Drug treatments; Pituitary Adenylate Cyclase-Activating Polypeptide
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00609-7

A pituitary adenylate cyclase-activating polypeptide (PACAP) activates PACAP and vasoactive intestinal peptide (VIP) receptors. We investigated the effects of PACAP-38 on the sinus rate and atrial contractile force in isolated, blood-perfused dog heart preparations and the stimulation by PACAP-38 of the parasympathetic nerve fibers. PACAP-38 (3–1000 pmol) caused positive and/or negative chronotropic responses and it dose dependently increased atrial and ventricular contractile force. The positive cardiac responses to PACAP-38 unlike those to VIP were much less than the positive responses to norepinephrine. Atropine inhibited the negative chronotropic responses to PACAP-38 and augmented the positive chronotropic and inotropic responses. Physostigmine potentiated the negative cardiac responses to PACAP-38 and acetylcholine. After physostigmine treatment, additionally, tetrodotoxin blocked the negative cardiac responses to PACAP-38 and intracardiac parasympathetic nerve stimulation. Propranolol did not inhibit the positive cardiac responses to PACAP-38 in atropine-treated atria. PACAP-(6–38) (1 and 3 nmol), an antagonist of PACAP-38, did not affect the cardiac responses to 100 pmol of PACAP-38. These results suggest that (1) PACAP-38 directly increases sinus rate and atrial contractile force and (2) PACAP-38 activates parasympathetic nerves and causes negative chronotropic and inotropic responses in the dog heart.