The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria
The aim of the present study was to investigate whether or not thyroxine (T(4)) treatment affects K(B), the equilibrium dissociation constant of the antagonist-receptor complex, for the interaction between CPX, a selective and competitive orthosteric antagonist, and the guinea pig atrial A1 adenosine receptor A1 receptor). The inotropic response to adenosine, a nonselective adenosine receptor agonist, or CPA, a selective A1 receptor agonist, was investigated in the absence or presence of CPX in paced left atria isolated from 8-day solvent- or T(4)-treated guinea pigs. To obtain K(B) values, adenosine and CPA concentration-response curves were evaluated by Schild analysis. CPA but not adenosine obeyed the requirements of the Schild analysis to provide correct K(B) values for CPX. According to the CPA concentration-response curves, affinity of CPX for the hyperthyroid guinea pig atrial A1 receptor (K(B) = 44.16 nM) was lower than that for the euthyroid one (K(B) = 16.63 nM). Regarding the intense reduction in the negative inotropic effect of adenosine and CPA in hyperthyroid atria, it is reasonable to assume that the moderate decrease in affinity of the guinea pig atrial A1 receptor is only in part responsible for the diminished A1 receptor-mediated effect in hyperthyroidism.