Different receptor subtypes mediate the dual presynaptic effects of 5-hydroxytryptamine on peripheral sympathetic neurones.

1. The aim of the present work was to characterize the presynaptic 5-HT receptors that mediate either the facilitation of the responses to nerve stimulation in the nictitating membrane of the cat or the inhibition of the responses to nerve stimulation in the guinea-pig atria. 2. In the nictitating membrane of the cat, the shift to the left in the frequency-response curves produced by 5-HT (0.1 microM) was prevented by the 5-HT3 receptor antagonists, metoclopramide (1 microM) and MDL 72222 (0.01 microM). 3. The facilitatory effect of 5-HT is also prevented by the 5-HT2 receptor antagonist, 0.01 microM ketanserin. Nevertheless, this drug reduced by itself the responses to both nerve stimulation and exogenous NA in the nictitating membrane. 4. In the guinea-pig isolated atria, the inhibitory effect of 5-HT on the chronotropic responses to cardioaccelerans nerve stimulation was mimicked by the mixed 5-HT1A + 5-HT1B + 5-HT1D receptor agonist 5-carboxamidotryptamine (5-CT 0.1 and 1 microM). The 5-HT1A receptor agonist 8-OH-DPAT (0.1 and 1 microM) did not modify the responses of the atria to the nerve stimulation. 5. The 5-HT2 receptor antagonists, ketanserin (0.01 and 0.1 microM) and cyproheptadine (1 microM), did not prevent the inhibitory effect of 5-HT in the guinea-pig atria. 6. The present results suggest that the facilitatory effects of 5-HT in the nictitating membrane of the cat are linked to the activation of 5-HT3 receptors whereas the inhibitory effects observed in the guinea-pig atria are mediated by 5-HT1-like receptors.