Interaction between histamine and clonidine in isolated guinea-pig atria.

1. This study investigates the chronotropic and inotropic effects of clonidine and its interaction with histamine in spontaneously beating and electrically driven isolated guinea-pig atria. 2. Clonidine (up to 100 microM) did not modify the force of contraction in either spontaneously beating or paced atria. 3. Clonidine increased the rate of beating, having a lower maximal effect (43 +/- 5%) and a higher EC50 (15.7 +/- 4 microM) than histamine (Emax = 100%; EC50 = 1.47 +/- 0.1 microM). 4. The positive chronotropic effect of clonidine was unchanged after clemizole, phentolamine, propranolol and atropine but was competitively antagonized by cimetidine (pA2 = 6.87 +/- 0.18). 5. Concentration-response curves for clonidine in the presence of several concentrations of histamine, and for histamine in the presence of several concentrations of clonidine, were constructed and the displacements observed with respect to the control curves in each case fit the competitive dualism model. 6. These results demonstrate that clonidine behaves as a partial agonist of the histamine H2-receptor in isolated guinea-pig atria.