Pertussis toxin sensitive and insensitive effects of adenosine and carbachol in murine atria overexpressing A1‐adenosine receptors

摘要: It was investigated how A1-adenosine receptor overexpression alters the effects of carbachol on force contraction and beating rate in isolated murine atria. Moreover, influence pertussis toxin inotropic chronotropic adenosine overexpressing atria studied. Adenosine alone exerted negative electrically driven left atrium or spontaneously right wild-type mice. These were abolished reversed by pre-treatment animals with which can interfere signal transduction through G-proteins. Adenosine positive but receptors from transgenic mice. The qualitatively unaltered whereas after toxin. Qualitatively similar for noted presence isoprenaline, β-adrenoceptor agonist. It is concluded that also affects other heptahelical, G-protein coupled like M-cholinoceptor heart. The not mediated via sensitive G-proteins. Keywords: receptors, chronotropy, inotropy, M-cholinoceptors, mice Introduction Adenosine (ado) generated heart response to stimuli such as hypoxia β-adrenergic stimulation (Bardenheuer et al., 1987; Berne, 1983). Adenosine exerts (Ralevic & Burnstock, 1998; Schrader 1977; Shryock Belardinelli, 1997), receptor. In addition A2a-, A2b- A3-adenosine have been detected (Boknik 1997; Reppert 1991; Salvatore 1993). most mammals (guinea-pig, mouse, man, rat) ado reduces when given (Bohm 1984; 1985; 1989; Dobson, 1983; Drury Szent-Gyorgyi, 1929). isoprenaline a effect many mammalian species 1998). (and ventricle stimulation) may involve inhibition adenylyl cyclase activity, cAMP-dependent protein kinase, activation phosphatases, phospholipase C opening ion channels (for review: Stein More specifically, be due voltage dependent KAch-channels, subsequent shortening action potential duration therefore less time influx Ca2+ (Belardinelli Isenberg, Thus, cell, acting myofilaments. Transgenic mice engineered overexpress (A1-AR) selectively (Matherne 1997). significantly more resistant functional metabolic ischaemia their overexpressed A1-AR Headrick addition, mimicked ischaemic preconditioning hearts (Morrison 2000). This cardioprotection ATP-sensitive potassium (Headrick 2000). In our previous work we demonstrated reduce contractility atrial preparations mice. (in this called mice) still reduced preparations. However, raised (positive effect) (Neumann 1999). conceivable reversal could reside at level alterations post-receptor pathway common muscarinic cholinoceptor. Therefore studied parallel work. The direct indirect (carb) are inhibitory Gi-proteins, covalently modified blocked 1986; 1988; Kurachi Neumann 1994). The purpose study investigate whether influences (by carb) atrium. Furthermore, wanted know carb (ptx) A1-AR.