Influence of 5-HT1A receptor agonists on sympathetic and parasympathetic nerve activity.
Activity in central sympathetic pathways can be modified by stimulating central alpha 2-adrenoceptors, e.g., with clonidine, or, more recently, by stimulating central 5-hydroxytryptamine (5-HT1A) receptors. Stimulation of 5-HT1A receptors causes central sympathoinhibition and an increase in cardiac vagal drive, which results in a profound fall in blood pressure. However, the central sympathoinhibition observed with 5-HT1A agonists such as 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] is not uniform for all regional sympathetic outflows, renal outflow being the most sensitive. The classical centrally acting antihypertensive drugs, the alpha 2-adrenoceptor agonists, also cause differential sympathoinhibition, but cardiac rather than renal nerve activity is the most sensitive. Now, if a 5-HT1A agonist is combined with an alpha 1-adrenoceptor antagonist, e.g., urapidil, then uniform central sympathoinhibition is observed. 5-HT1A agonists also differ from alpha 2-adrenoceptor agonists in that they increase central vagal drive. Further, 5-HT-containing boutons have been shown to make synaptic contact with cardiac vagal motoneurons (CVMs), and there is also a high density of 5-HT1A binding in the brain nuclei containing these CVMs. This suggests that there is an excitatory 5-HT-containing pathway that innervates CVMs and involves the activation of 5-HT1A receptors. In this respect, cardiopulmonary afferent fiber activation of CVMs is blocked by central administration of 5-HT1A receptor antagonists. In conclusion, 5-HT1A receptors are important in the patterning of sympathetic outflow by central cardiovascular pathways and are involved in the central control of parasympathetic outflow, at least to the heart.
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, England.
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D000818:Animals; D006801:Humans; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D011985:Receptors, Serotonin