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Dual effect of ATP and UTP on rat atria: which types of receptors are involved?

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Abstract

The effects of adenine compounds and UTP were examined in electrically driven rat left atria.

ATP, ADP, AMP, adenosine and UTP caused a dual inotropic effect: first a rapid decrease in contractility, and second an increase in contractile tension. α,β-Methylene ATP caused an increase in contractile tension only, whereas 2-methylthio-ATP only induced a negative inotropic effect. 1,3-Dipropyl-8-cyclopentylxanthine inhibited the negative effects of ATP and adenosine, whereas 3,7-dimethyl-l-propargylxanthine did not influence the effects of ATP. Suramin but not reactive blue 2 antagonized the positive inotropism induced by ATP and α,β-methylene ATP. Suramin also abolished the positive inotropic effect induced by UTP.

These results demonstrate that ATP may induce negative inotropism directly by an action on A1-adenosine receptors and positive inotropism by an action on P2x-purinoceptors. UTP induces a positive inotropic effect mediated by Suramin-sensitive receptors.

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References

  • Brashear R, Mandelbaum I, Ross JC (1970) Selected cardiovascular effects of adenosine diphosphate. Am Heart J 80:63–69

    Article  CAS  PubMed  Google Scholar 

  • Brückner R, Fenner A, Meyer W, Nobis TM, Schmitz W, Scholz H (1985) Cardiac effects of adenosine and adenosine analogs in guinea-pig atrial and ventricular preparations: evidence against a role of cyclic AMP and cyclic GMP. J Pharmacol Exp Ther 234:766–774

    PubMed  Google Scholar 

  • Bruns RF, Fergus JH, Badger EW, Bristol JA, Santay LA, Hartman JD, Hays SJ, Huang CC (1987) Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes. Naunyn Schmiedebergs Arch Pharmacol 335:59–63

    Article  CAS  PubMed  Google Scholar 

  • Burnstock G (1978) A basis for distinguishing two types of purinergic receptor. In: Straub RW, Bolis L (eds) Cell membrane receptors for drugs and hormones: a multidisciplinary approach. Raven Press, New York, pp 107–118

    Google Scholar 

  • Burnstock G, Kennedy C (1985) Is there a basis for distinguishing two types of P2-purinoceptors?. Gen Pharmacol 16:433–440

    Article  CAS  PubMed  Google Scholar 

  • Burnstock G, Meghji P (1981) Distribution of P1- and P2-purinoceptors in the guinea-pig and frog heart. Br J Pharmacol 73:879–885

    Article  CAS  PubMed  Google Scholar 

  • Burnstock G, Warland JJI (1987) P2-purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P2y but not the P2x-purinoceptor. Br J Pharmacol 90:383–391

    Article  CAS  PubMed  Google Scholar 

  • Chiba S, Himori N (1975) Different inotropic responses to adenosine on the atrial and ventricular muscle of the dog heart. Jpn J Pharmacol 25:489–491

    Article  CAS  PubMed  Google Scholar 

  • Collis MG, Pettinger SJ (1982) Can ATP stimulate P1-receptors in guinea-pig atrium without conversion to adenosine? Eur J Pharmacol 81:521–529

    Article  CAS  PubMed  Google Scholar 

  • Daly JW, Padgett WL, Shamim MT (1986) Analogues of caffeine and theophylline: effect of structural alterations on affinity at adenosine receptors. J Med Chem 29:1305–1308

    Article  CAS  PubMed  Google Scholar 

  • Davidson JS, Wakefield IK, Sohnius U, Van Der Merwe PA, Millar RP (1990) A novel extracellular nucleotide receptor coupled to phosphoinositidase C in pituitary cells. Endocrinology 126:80–87

    Article  CAS  PubMed  Google Scholar 

  • Dorigo P, Gaion RM, Maragno I (1988) Negative and positive influences exerted by purine compounds on isolated guinea-pig atria. J Auton Pharmacol 8:191–196

    Article  CAS  PubMed  Google Scholar 

  • Druy AN, Szent-Gybrgyi A (1929) The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol 68:213–237

    Google Scholar 

  • Dubyak GR (1991) Signal transduction by P2-purinergic receptors for extracellular ATP. Am J Respir Cell Mol Biol 4:295–300

    Article  CAS  PubMed  Google Scholar 

  • Dunn PM, Blakeley AGH (1988) Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens. Br J Pharmacol 93:243–245

    Article  CAS  PubMed  Google Scholar 

  • Fleetwood G, Gordon JL (1987) Purinoceptors in the rat heart. Br J Pharmacol 90:219–227

    Article  CAS  PubMed  Google Scholar 

  • Flitney FW, Singh J (1980) Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides. J Physiol 304:21–42

    CAS  PubMed  Google Scholar 

  • Goto M, Yatani A, Tsuda Y (1976) Effects of ATP on the membrane currents and tension components of bullfrog atrial muscle. J Physiol Soc Japan 38:503–506

    CAS  Google Scholar 

  • Häussinger D, Stehle T, Gerok W (1987) Actions of extracellular UTP and ATP in perfused rat liver: a comparative study. Eur J Biochem 167:65–71

    Article  PubMed  Google Scholar 

  • Hoyle CHV, Knight GE, Burnstock G (1990) Suramin antagonizes responses to P2-purinoceptor agonists and purinergic nerve stimulation in the guinea-pig urinary bladder and taenia coli. Br J Pharmacol 99:617–621

    Article  CAS  PubMed  Google Scholar 

  • Hutchison AJ, Webb RL, Oei HH, Ghai GR, Zimmerman MB, Williams M (1989) CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity. J Pharmacol Exp Ther 251:47–55

    CAS  PubMed  Google Scholar 

  • Jahnel U, Nawrath H (1989) Characterization of adenosine receptors in guinea-pig isolated left atria. Br J Pharmacol 97:1182–1190

    Article  CAS  PubMed  Google Scholar 

  • von Kügelgen I, Haussinger D, Starke K (1987) Evidence for a vasoconstriction-mediating receptors for UTP, distinct from the P2 purinoceptor, in rabbit ear artery. Naunyn Schmiedebergs Arch Pharmacol 336:556–560

    Article  Google Scholar 

  • von Kügelgen I, Bultmann R, Starke K] (1989a) Effects of suramin and α,β-methylene ATP indicate noradrenaline-ATP co-transmission in the response of the mouse vas deferens to single and low frequency pulses. Naunyn Schmiedebergs Arch Pharmacol 340:760–763

    Google Scholar 

  • von Kügelgen I, Schoffel E, Starke K (1989b) Inhibition by nucleotides acting at presynaptic P2-receptors of sympathetic neuro-effector transmission in the mouse isolated vas deferens. Naunyn Schmiedebergs Arch Pharmacol 340:522–532

    Google Scholar 

  • von Kügelgen I, Bültmann R, Starke K (1990) Interaction of adenine nucleotides, UTP, and suramin in mouse vas deferens: suramin-sensitive and suramin-insensitive components in the contractile effect of ATP. Naunyn Schmiedebergs Arch Pharmacol 342:198–205

    Article  Google Scholar 

  • Kukovetz WR, Pöch G (1970) Cardiostimulatory effects of cyclic 3′-5′-adenosine monophosphate and its acylated derivatives. Naunyn Schmiedebergs Arch Pharmacol 266:236–254

    Article  CAS  PubMed  Google Scholar 

  • Legssyer A, Poggioli J, Renard D, Vassort G (1988) ATP and other adenine compounds increase mechanical activity and inositol trisphosphate production in rat heart. J Physiol 401:185–199

    CAS  PubMed  Google Scholar 

  • Lohse MJ, Klotz KN, Lindenborn-Fotinos J, Reddington M, Schwabe U, Olsson RA (1987) 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) a selective high affinity antagonist radioligand for A1 adenosine receptors. Naunyn-Schmiedebergs Arch Pharmacol 336:204–210

    Article  CAS  PubMed  Google Scholar 

  • Mantelli L, Amerini S, Filippi S, Ledda F (1993) Blockade of adenosine receptors unmasks a stimulatory effect of ATP on cardiac contractility. Br J Pharmacol 109:1268–1271

    Article  CAS  PubMed  Google Scholar 

  • Meinertz T, Nawrath H, Scholz H (1973) Influence of cyclization and acyl substitution on the inotropic effects of adenine nucleotides. Naunyn Schmiedebergs Arch Pharmacol 278:165–178

    Article  CAS  PubMed  Google Scholar 

  • Moody CJ, Meghji P, Burnstock G (1984) Stimulation of P1-purino-ceptors by ATP depends partly on its conversion to AMP and adenosine and partly on direct action. Eur J Pharmacol 97:47–54

    Article  CAS  PubMed  Google Scholar 

  • O’Connor SE (1992) Recent developments in the classification and functional significance of receptors for ATP and UTP, evidence for nucleotide receptors. Life Sci 50:1657–1664

    Article  PubMed  Google Scholar 

  • O’Connor SE, Dainty IA, Leff P (1991) Further subclassification of ATP receptors based on agonist studies. Trends Pharmacol Sci 12:137–141

    Article  PubMed  Google Scholar 

  • Saïag B, Milon D, Allain H, Rault B, Van Den Driessche J (1990) Constriction of the smooth muscle of rat tail and femoral arteries and dog saphenous vein is induced by uridine triphosphate via “pyrimidinoceptors”, and by adenosine triphosphate via P2x purinoceptors. Blood Vessels 27:352–364

    PubMed  Google Scholar 

  • Schlicker E, Urbanek E, Gothert M (1989) ATP, α,β-methylene ATP and suramin as tools for characterization of vascular P2x receptors in the pithed rat. J Auton Pharmacol 9:357–366

    Article  CAS  PubMed  Google Scholar 

  • Seifert F, Schultz G (1989) Involvement of pyrimidinoceptors in the regulation of cell functions by uridine and by uracil nucleotides. Trends Pharmacol Sci 10:365–369

    Article  CAS  PubMed  Google Scholar 

  • Stone TW (1991) Receptors for adenosine and adenine nucleotides. Gen Pharmacol 22:25–31

    Article  CAS  PubMed  Google Scholar 

  • Van Calker D, Muller M, Hamprecht B (1979) Adenosine regulates, via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 33:999–1005

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, University of Padova, Largo E. Meneghetti 2, 1-35131, Padova, Italy

    Guglielmina Froldi, Luisa Pandolfo, Alessandro Chinellato, Eugenio Ragazzi, Laura Caparrotta & Giuliana Fassina

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  1. Guglielmina Froldi
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  2. Luisa Pandolfo
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  3. Alessandro Chinellato
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  4. Eugenio Ragazzi
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  5. Laura Caparrotta
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  6. Giuliana Fassina
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Correspondence to: G. Froldi at the above address

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Froldi, G., Pandolfo, L., Chinellato, A. et al. Dual effect of ATP and UTP on rat atria: which types of receptors are involved?. Naunyn-Schmiedeberg’s Arch Pharmacol 349, 381–386 (1994). https://doi.org/10.1007/BF00170884

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  • DOI: https://doi.org/10.1007/BF00170884

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