Effects of anti-peptide antibodies against human M2 muscarinic receptors on cardiac function in rats in vivo.

The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on cardiac function in rats in vivo were studied. These effects were compared with those of the muscarinic receptor agonist, carbachol (Carb). It was shown that: (1) both Carb and Ab administered intravenously in the same doses of 0.4 nmol, 1.0 nmol, and 2.0 nmol were able to inhibit the maximal rate of rise of ventricular pressure (+dp/dt max) in a dose-dependent manner. (2) The isoproterenol (Iso)-induced increase in HR and +dp/dt max were also markedly inhibited by Carb and Ab. Administration of 1.0 nmol Carb decreased the Iso-stimulated increase of HR from 13.6 +/- 2.0 to 4.9 +/- 0.7% and decreased the increase of +dp/dt max from 27.9 +/- 3.2 to 4.8 +/- 0.6%, respectively; whereas Ab decreased the HR to 6.5 +/- 1.1% and +dp/dt max to 13.5 +/- 1.2%, respectively. (3) Both the inhibitory effects of Carb and Ab could be significantly blocked by atropine (1.4 nmol). These findings suggest that the Ab display a stimulatory muscarinic activity similar to Carb in inhibiting the cardiac function as evidenced by its negative chronotropic and inotropic effects.