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

Abstract

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.