Identification of presynaptic 5-HT1 autoreceptors in pig brain cortex synaptosomes and slices

Abstract

Pig brain cortex synaptosomes and slices preincubated with 3H-5-hydroxytryptamine (3H-5-HT) were superfused with physiological salt solution containing citalopram (an inhibitor of 5-HT uptake), and the effects of indolethylamines and 5-HT receptor antagonists on the potassium- or electrically evoked 3H overflow were determined. The potassium (25 mmol/l)-evoked tritium overflow from cortex synaptosomes was inhibited by 5-HT; the inhibitory effect of 5-HT was counteracted by metitepine, which, by itself, did not affect the evoked overflow. 5-Methoxytryptamine (examined in the absence of citalopram) also produced an inhibition of the evoked overflow. In cortex slices, the electrically (3 Hz) evoked overflow was inhibited by 5-HT and 5-carboxamidotryptamine. The inhibitory effect of 5-HT was antagonized by metitepine, which, given alone, increased the evoked overflow, but was not attenuated by ketanserin and ICS 205-930 ([3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester), which, by themselves, did not influence the evoked overflow. The present results suggest that the serotoninergic nerve fibres of the pig brain cortex are endowed with presynaptic 5-HT1 receptors, which can be activated by endogenous and exogenous 5-HT.

Anpirtoline, a novel, highly potent 5‐HT1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

“…in superfused rat and pig brain cortex slices preincubated with [3H]-5-HT. The electrically evoked tritium overflow in either tissue is tetrodotoxinsensitive and Ca2 +-dependent and, thus, represents quasiphysiological 5-HT release (Fink et al, 1988;Gbthert, 1980). 5-HT release in either tissue is subject to modulation via inhibitory presynaptic autoreceptors (Moret, 1985;Timmer- Middlemiss, 1988;Starke et al, 1989).…”

Functional characterization of the 5‐HT terminal autoreceptor in the guinea‐pig brain cortex

“…Receptor agonist and antagonist potencies indicate that the 5-HT terminal autoreceptors in the latter species correlate with 5-HTlD receptor binding (Fink et al, 1988;Middlemiss, 1988;Hoyer & Middlemiss, 1989;Schlicker et al, 1989;Starke et al, 1989;Limberger et al, 1991;Maura et al, 1993).…”

The Inhibitory Effect of Trifluoromethylphenylpiperazine on [3H]Acetylcholine Release in Guinea Pig Hippocampal Synaptosomes Is Mediated by a 5‐Hydroxytryptamine1 Receptor Distinct from 1A, 1B, and 1C Subtypes

“…The pharmacological characteristics of the autoreceptor, distinct from those of 5-HT2, 5-HT3, ~-H T I A , ~-H T I B , and 5-HTlc sites and corresponding to those of the 5-HTID receptor subtype, in guinea pig (Middlemiss and Bremer, 1987;Middlemiss et al, 1988;Hoyer and Middlemiss, 1989), human (Galzin et al, 1988), or pig (Schlicker et al, 1989) brain tissue resemble those of the heterologous presynaptic receptor that regulates the release of ['HIACh from the cholinergic nerve terminals. However, methiotepine and 5-CT are potent drugs at autoreceptors (Middlemiss and Bremer, 1987;Fink et al, 1988), whereas they show a weak activity at heteroreceptors, a result suggesting that autoand heteroreceptors are not identical.…”