Pituitary adenylate cyclase-activating polypeptide stimulates cardiodilatin/atrial natriuretic peptide (CDD/ANP-(99-126) secretion from cultured neonatal rat myocardiocytes. 1995

I Bäsler, and M Kuhn, and W Müller, and W G Forssmann
Lower Sarony Institute for Pepride Research (IPF), Hannover Medical School, Germany.

It has been reported that the highly homologous neuropeptides pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP) exert similar cardiovascular effects in vivo. In the present study we compared the effects of these neuropeptides on myocardial cyclic AMP content and the release of immunoreactive CDD/ANP-(99-126) (atrial natriuretic peptide). In cultured neonatal rat cardiomyocytes PACAP and VIP evoke concentration-dependent increases in intracellular cyclic AMP content but responses to VIP are markedly less. PACAP stimulates the release of CDD/ ANP-(99-126) in a concentration-dependent manner with a threshold concentration of 1 nM, and up to a 6-fold increase in basal secretion at 1 microM PACAP. In contrast. VIP had no effect on the release of CDD/ANP. Pretreatment of cells with the competitive PACAP-antagonist, PACAP-6-38 (1 microM), significantly reduces the effects of PACAP on intracellular cyclic AMP and on CDD/ANP-(99-126) secretion and abolishes the effects of VIP on cyclic AMP. Pretreatment with VIP-receptor antagonist (1 microM) prevents the cyclic AMP-response to VIP while increases in cyclic AMP as well as stimulation of CDD/ANP-(99-126) release by PACAP are not affected. It is concluded that both neuropeptides directly influence cardiac myocytes through an increase in intracellular cyclic AMP. Release of CDD/ ANP-(99-126) by PACAP may be involved in the decrease in blood pressure that follows intravenous administration of this peptide. The higher potency of PACAP to induce cyclic AMP synthesis, its stimulating effect on the release of CDD/ANP-(99-126) and the finding that the VIP-receptor antagonist inhibits responses to VIP but not to PACAP suggest that PACAP activates cardiac myocytes through a PACAP-specific receptor.

UI MeSH Term Description Entries
D009124 Muscle Proteins The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN. Muscle Protein,Protein, Muscle,Proteins, Muscle
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D009320 Atrial Natriuretic Factor A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS. ANF,ANP,Atrial Natriuretic Peptide,Atrial Natriuretic Peptides,Atriopeptins,Auriculin,Natriuretic Peptides, Atrial,ANF (1-126),ANF (1-28),ANF (99-126),ANF Precursors,ANP (1-126),ANP (1-28),ANP Prohormone (99-126),ANP-(99-126),Atrial Natriuretic Factor (1-126),Atrial Natriuretic Factor (1-28),Atrial Natriuretic Factor (99-126),Atrial Natriuretic Factor Precursors,Atrial Natriuretic Factor Prohormone,Atrial Natriuretic Peptide (1-126),Atrial Pronatriodilatin,Atriopeptigen,Atriopeptin (1-28),Atriopeptin (99-126),Atriopeptin 126,Atriopeptin Prohormone (1-126),Cardiodilatin (99-126),Cardiodilatin Precursor,Cardionatrin I,Cardionatrin IV,Prepro-ANP,Prepro-CDD-ANF,Prepro-Cardiodilatin-Atrial Natriuretic Factor,Pro-ANF,ProANF,Proatrial Natriuretic Factor,Pronatriodilatin,alpha ANP,alpha-ANP Dimer,alpha-Atrial Natriuretic Peptide,beta-ANP,beta-Atrial Natriuretic Peptide,gamma ANP (99-126),gamma-Atrial Natriuretic Peptide,Natriuretic Peptide, Atrial,Peptide, Atrial Natriuretic,Peptides, Atrial Natriuretic,Prepro ANP,Prepro CDD ANF,Prepro Cardiodilatin Atrial Natriuretic Factor,Pro ANF,alpha ANP Dimer,alpha Atrial Natriuretic Peptide,beta ANP,beta Atrial Natriuretic Peptide,gamma Atrial Natriuretic Peptide
D009479 Neuropeptides Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. Neuropeptide
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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