Naunyn-Schmiedeberg's Arch Pharmacol (1994) 349:381-386 Naunyn-Schmiedeberg's Archivesof Pharmacology © Springer-Verlag 1994 Dual effect of ATP and UTP on rat atria: which types of receptors are involved? Guglielmina Froldi, Luisa Pandolfo, Alessandro Chinellato, Eugenio Ragazzi, Laura Caparrotta, Giuliana Fassina Department of Pharmacology, University of Padova, Largo E. Meneghetti 2, 1-35131 Padova, Italy Received: 3 August 1993/Accepted: 7 December 1993 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, a,~Methylene ATP caused an increase in contractile tension only, whereas 2-methylthio-ATP only induced a negative in- otropic effect. 1,3-Dipropyl-8-cyclopentylxanthine inhib- ited 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 antago- nized the positive inotropism induced by ATP and a,fl-methylene ATE Suramin also abolished the positive inotropic effect induced by UTP. These results demonstrate that ATP may induce nega- tive inotropism directly by an action on Al-adenosine re- ceptors and positive inotropism by an action on P2x- purinoceptors. UTP induces a positive inotropic effect mediated by suramin-sensitive receptors. Key words: ATP - UTP - Adenosine - Suramin - Pl-purinoceptors - P2-purinoceptors - Positive ino- tropism - Rat left atria Introduction The effects of adenine nucleotides and nucleosides have been extensively studied in many different tissues, mainly vascular vessels, but few data are available on myocardial tissue. Adenosine 5'-triphosphate (ATP) and adenosine chiefly induce negative inotropic effects on the mammali- an heart (Drury and Szent-GyOrgyi 1929; Meinertz et al. 1973; Burnstock and Meghji 1981; Fleetwood and Gor- don 1987). However, an increase in contractile tension by adenine compounds and/or adenosine has also been ob- served in frog (Goto et al. 1976; Flitney and Singh 1980; Burnstock and Meghji 1981) and mammalian heart (Brashear et al. 1970; Kukovetz and P0ch 1970; Chiba Correspondence to: G. Froldi at the above address and Himori 1975; Brt~ckner et al. 1985; Dorigo et al. 1988; Legssyer et al. 1988). Authors have generally paid little attention to the positive effect, because it has often been considered simply as the recovery from negative in- otropism (Jahnel and Nawrath 1989). Burnstock (1978) proposed that the biological effects of adenine nucleotides and adenosine are mediated by two receptor types. Those activated mainly by adenosine are termed Pl-purinoceptors and are subdivided into A I- and A2-adenosine receptors (Van Calker et al. 1979). Those activated mainly by ATP are termed P2-purino- ceptors. P2-purinoceptors are subdivided into P2x and Pzy on the basis of the rank order of potency of ATP analogues (Burnstock and Kennedy 1985). The P2x- receptor is activated with a potency order a,fl-me- thylene ATP (a,fl-meATP) > ATP > 2-methylthio ATP (2-MeSATP), whereas the P2y-receptor is activated with an inverse potency order (Burnstock and Kennedy 1985). Other subtypes of receptor were later postulated in differ- ent tissues as a consequence of atypical purinoceptor sen- sitivity (Dubyak 1991; Stone 1991). Few authors have noted the effects induced by the py- rimidine UTP in mammalian tissues. Moreover, the type of receptor involved is still unclear. Some reports indicate that UTP acts by activation of a nucleotide receptor com- mon to ATP and UTP (Davidson et al. 1990; O'Connor et al. 1991); others, that it acts through a separate pyrimidine receptor (H~iussinger et al. 1987; von Kt~gelgen et al. 1987; Seifert and Schultz 1989; Sa'iag et al. 1990); still others, that it acts at the P2x-purinoceptor (yon Kt~gelgen et al. 1987, 1989b). The purpose of the present study was to examine the effects of ATP, both negative and positive, and the recep- tors involved, in isolated rat atria. The positive inotropic effect induced by UTP and the type of receptor were also evaluated. Methods Male rats (Wistar, 250-350g) were sacrificed, after anaesthesia through inhalation of methoxyflurane, by cervical dislocation and the