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Abstract
The experimental facts presented here allow us to establish a relationship between DA motor effects on isolated rat duodenum, studied in a previous work, (excitomotor between 10−9 M and 10−5 M and inhibitor beyond 10−5 M) and the functional aptitude of this duodenum to answer to 5-HT: 5-HT excito-motor effects are amplified by DA at concentrations ≤ 2.6 × 10−6 M and on the contrary antagonized by DA at concentrations above 5 × 10−6 M. On the other hand, DA excito-motor effects do not appear on 5-HT-desensitized duodenums.
The study of 5-HT dose-response curves in the presence of different concentrations of DA suggests that the amplification of serotonergic effects observed with small DA concentrations can be possibly related to the additional effects of 5-HT on its own receptors and of DA on another receptor.
The receptor involved in DA excito-motor action seems to be closely related to the 5-HT receptor since its effects are blocked by the same molecules (methysergide, cyproheptadine) and since DA excito-motor action is no more evident on 5-HT-desensitized duodenums, but several arguments support the specificity of this receptor for DA (though it is not blocked by haloperidol). Some of its effects are in line with those of DA receptors made conspicuous in other territories and not blocked by haloperidol: central and human colon receptors.
On the contrary, DA used at high concentrations (≥ 5 × 10−6 M) seems to be able to occupy serotonergic sites, preventing 5-HT access to its receptors until its concentration is high enough to displace DA. From a functional point of view, this antagonistic effect of DA at high concentrations against 5-HT excito-motor effects could facilitate α- and β-mediated inhibitory effects.