ATP and other adenine compounds increase mechanical activity and inositol trisphosphate production in rat heart.
1. The effects of adenosine 5'-triphosphate (ATP) and other adenine compounds were examined on rat papillary and right ventricular muscles in the presence of 10 microM-propranolol, 10 microM-atropine and 0.1 microM-prazosin or 10 microM-phentolamine. 2. Adenosine, adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), ATP and alpha,beta-methylene ATP (APCPP) produced small positive inotropic effects, sometimes preceded by transient negative effects. 3. 8-Phenyltheophylline (8-PT), a P1-purinoceptor antagonist antagonized the negative effects and increased the positive inotropy induced by ATP and adenosine. 4. In the presence of APCPP, a P2-purinergic agonist, ATP had only negative inotropic effects. 5. Adenosine and ATP increased inositol 1, 4, 5- and inositol 1, 3, 4-trisphosphate as well as inositol mono- and bisphosphate formation. Maximal effects were obtained at concentrations of 0.5 mM. 6. APCPP increased inositol phosphate formation while 8-PT did not prevent the effects of adenosine and ATP. 7. It is suggested that P2-purinoceptor activation induces both a positive inotropy and an increase in inositol-lipid metabolism in rat ventricular muscles.
Legssyer
A
A
Unité de Recherches de Physiologie Cellulaire Cardiaque INSERM U-241, Université Paris, Orsay, France.
Poggioli
J
J
Renard
D
D
Vassort
G
G
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013403:Sugar Phosphates / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000227:Adenine Nucleotides; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013565:Sympatholytics; D001285:Atropine; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate