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.
Ramage
A G
AG
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, England.
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