title: Multiple opioid receptors mediate the hypotensive response induced by central 5-HT(3) receptor stimulation.
abstract: The aim of the present work was to investigate the role of brain μ, κ and δ opioid receptors in the central serotonergic mechanisms regulating blood pressure in rats. The data obtained show that: (1) pharmacological activation of central 5-HT(3) receptors yields a significant decrease in blood pressure; (2) the blockade of those receptors by a selective antagonist induces an acute hypertensive response; (3) the pharmacological blockade of central opioid receptors by three different opioid antagonists exhibiting variable degrees of selectivity to μ, κ and δ opioid receptors always suppressed the hypotensive response induced by central 5-HT(3) receptor stimulation; (4) the blockade of opioid receptors by the same opioid antagonists that impaired the hypotensive effect of central 5-HT(3) receptor stimulation failed to modify blood pressure in animals not submitted to pharmacological manipulations of central 5-HT(3) receptor function. It is shown that a 5-HT(3) receptor-dependent mechanism seems to be part of the brain serotonergic system that contributes to cardiovascular regulation since the hypertensive response observed after ondansetron administration indicates that central 5-HT(3) receptors exert a tonic inhibitory drive on blood pressure. Furthermore, the data obtained here clearly indicate that the hypotensive response observed after pharmacological stimulation of central 5-HT(3) receptors depends on the functional integrity of brain μ, κ and δ opioid receptors, suggesting that a functional interaction between serotonergic and opiatergic pathways in the brain is part of the complex, multifactorial system that regulates blood pressure in the central nervous system.
authors.affiliation: Department of Physiology, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil. josmara@ufba.br
authors.forename: J B
authors.initials: JB
authors.lastname: Fregoneze
authors.forename: E F
authors.initials: EF
authors.lastname: Oliveira
authors.forename: V F
authors.initials: VF
authors.lastname: Ribeiro
authors.forename: H S
authors.initials: HS
authors.lastname: Ferreira
authors.forename: E
authors.initials: E
authors.lastname: De Castro E Silva
mesh_terms: D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology
chemical_list: D001645:Biguanides; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D009270:Naloxone; D017294:Ondansetron; D009271:Naltrexone; C065734:1-(3-chlorophenyl)biguanide; C055382:naltrindole