Analysis of the atypical characteristics of adenosine receptors mediating negative inotropic and chronotropic responses of guinea-pig isolated atria and papillary muscles

1 Adenosine receptor(s) mediating negative inotropy of paced left atria, is oprenaline-stimulated paced left atria and papillary muscles, and negative chronotropy of spontaneously beating right atria were characterized. 2 Isometric tension of guinea-pig isolated paced left atria and left ventri cular papillary muscles and rate of contraction of spontaneously beating ri ght atria were recorded. Papillary muscles were prestimulated with isoprena line (1 x 10(-8) M). Concentration-response curves (CRCs) for tension or ra te reduction by N-6-cyclopentyladenosine (CPA), the stereoisomers of N-6-(2 -phenylisopropyl)adenosine ((+)-PIA and (-)-PIA), 5'-(N-carboxamido)adenosi ne (NECA), N-6-2-(4-aminophenyl)ethyladenosine (APNEA) and N-6-(3-iodobenzy l)adenosine-5'-N-methyuromide (IB-MECA) revealed a potency order of CPA =(- )-PIA>NECA in right atria and papillary muscles, which is consistent with i nvolvement of A(1)-receptors. The potency order in left atria was CPA = NEC A > (-)-PIA > (+)-PIA > APNEA, which is not typical of A(1) adenosine recep tors. Weak activity of APNEA and IB-MECA discounts involvement of A(3) rece ptors. 3 pA(2) values for the antagonism of CPA by s(p-sulfophenyl)theophylline (8 -SPT) were calculated from Schild plots (log concentration-ratio against lo g 8-SPT concentration), the unity slopes of which indicated competitive ant agonism. The pA(2) value in the papillary muscles was significantly higher than for atrial preparations, indicating a possible difference in receptor characteristics between atrial and papillary muscle responses. 4 In left and right atria there was a limit to the displacement of the CPA CRCs at higher concentrations of 8-SPT. The 8-SPT-resistant component of th e response is suggested to arise from duality of coupling of a common A(1) receptor through either different G proteins or G protein subunits to indep endent transduction pathways. The results with papillary muscles can be exp lained by a typical A(1) receptor coupled to a single transduction pathway.