Comparison of the pharmacological characteristics of 5 HT1 and 5 HT2 binding sites with those of serotonin autoreceptors which modulate serotonin release.

The abilities of various 5-hydroxytryptamine (5 HT) receptor agonists to inhibit the K+-evoked release of 3H-5 HT from prelabelled synaptosomal preparations of rat hypothalamus were studied. In addition, the abilities of various 5 HT receptor agonists and antagonists to compete with 3H-5 HT and 3H-spiperone binding to 5 HT1 and 5 HT2 sites, respectively, were determined. The orders of potency of the agonists for inhibiting K+-evoked 3H-5 HT release and for inhibiting 3H-5 HT and 3H-spiperone binding were then compared. Likewise, the abilities of the antagonists to block the inhibitory effect of 5 HT on its own K+-evoked release (data from previous studies) were compared to the affinities of these compounds for the 3H-5 HT and 3H-spiperone binding sites. A significant correlation was obtained between the effects of the agonists on K+-evoked 3H-5 HT release and 3H-5 HT binding but not 3H-spiperone binding. Furthermore, the antagonists which have been demonstrated to block the inhibitory effect of 5 HT on its own release (methiothepin, methysergide, metergoline and quipazine) had higher affinities for the 3H-5 HT binding site than the other antagonists. A similar correlation could not be made between antagonist activity at the 5 HT autoreceptor and affinity for the 3H-spiperone binding site. These results demonstrate that the 5 HT autoreceptor and the 5 HT1 binding site have similar pharmacological characteristics. On this basis, it is suggested that 5 HT autoreceptor and the 5 HT1 binding site may be related 5 HT receptor sites.