EFFECTS OF SEROTONIN AND METERGOLINE ON (125)[I]-IODOCYANOPINDOLOL BINDING PARAMETERS TO BETA-ADRENERGIC RECEPTORS IN RAT-BRAIN

Most ligands which have been employed to investigate the regulation of beta-adrenergic receptors (beta AR) under pathophysiological conditio ns and in response to pharmacological manipulations have also been sho wn to have affinity for 5-HT1B receptors. We examined the effects of s erotonin and metergoline (10 mu M) on I-125-iodocyanopindolol (ICYP, 5 -100 pM) binding to beta AR in rat frontal cortex and hippocampus memb ranes. In both brain regions, the presence of either serotonin or mete rgoline significantly lowered iodocyanopindolol dissociation constant (K-d) and maximum binding capacity (B-max). Isoproterenol displacement curves showed that the decrease in receptor density was primarily due to a significant decrease in the receptors in the low-conformational state. Thus, a significant fraction of the apparent ICYP binding to be ta AR in the low-conformational state was due to binding to 5-HT1B rec eptors. Neither serotonin nor metergoline had an effect on the agonist isoproterenol dissociation constant from beta AR in either conformati onal state. Published by Elsevier Science B.V./ECNP.