Kinetics of blockade of different receptors by chlorpromazine in rabbit stomach strips

Abstract

The kinetics of receptor blockade by chlorpromazine (5 X 10(-8) M) were studied on fundic strips from the rabbit stomach. Onset of blockade by chlorpromazine proceeds at nearly identical rates when carbamylcholine and histamine are the agonists (t1/2 = approximately 5 min) while occurring more slowly against phenylephrine (t1/2 = 41 min). Similarly, offset of blockade by chlorpromazine is faster against carbamycholine and histamine (t1/2 = 83 and 34 min, respectively) than against phenylephrine (t1/2 = 385 min). The pA2 values of chlorpromazine on the alpha-adrenergic, muscarinic and histaminic (H1) receptors are 8.96, 7.17, and 7.90, respectively. No correlation exists between the kinetics of blockade and the affinity of chlorpromazine for the receptors. It is suggested, therefore, that alpha-adrenoreceptors in the rabbit stomach are less accessible to chlorpromazine, or distributed differently within the tissue, than either the muscarinic or histaminic receptors.