The effect of pituitary adenylate cyclase activating polypeptide on cultured rat cardiocytes as a cardioprotective factor.
In the cardiovascular system, pituitary adenylate cyclase activating polypeptide (PACAP) exhibits not only vasodilation but also positive inotropic action by increasing cardiac output. Then the effect of PACAP in cultured cardiovascular cells was examined. In neonatal rat myocytes, PACAP evoked concentration-dependent increase in intracellular cyclic AMP content more potently than vasoactive intestinal polypeptide (VIP). However, in neonatal rat nonmyocytes, PACAP and VIP showed equal potency. The characterization of the subtype of PACAP/VIP receptors by RT-PCR analysis revealed that PAC1 receptor mRNA is dominantly present in the myocytes, but VPAC2 receptor mRNA is abundant in the nonmyocytes. In the myocytes, PACAP did not change the protein synthesis stimulated by endothelin or by itself. However, PACAP moderately stimulated the secretion of atrial natriuretic polypeptide (ANP). On the other hand, PACAP inhibited the protein synthesis and DNA synthesis of the nonmyocytes. These indicate that PACAP might be involved in the regulation of cardiac hypertrophy and fibrosis as a cardioprotective factor.
Sano
Hirofumi
H
National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Miyata
Atsuro
A
Horio
Takeshi
T
Nishikimi
Toshio
T
Matsuo
Hisayuki
H
Kangawa
Kenji
K
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; C495505:Adcyap1r1 protein, rat; D002316:Cardiotonic Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; C495511:Vipr2 protein, rat; D014660:Vasoactive Intestinal Peptide; D009320:Atrial Natriuretic Factor; D003094:Collagen; D000242:Cyclic AMP