Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The locus coeruleus (LC) is a noradrenergic nucleus that plays an important role in the ventilatory response to hypercapnia. This nucleus is densely innervated by serotonergic fibers and contains high density of serotonin (5-HT) receptors, including 5-HT(1A) and 5-HT(2). We assessed the possible modulation of respiratory response to hypercapnia by 5-HT, through 5-HT(1A) and 5-HT(2) receptors, in the LC. To this end, we determined the concentrations of 5-HT and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) in the LC after hypercapnic exposure. Pulmonary ventilation (VE: , plethysmograph) was measured before and after unilateral microinjection (100 nL) of WAY-100635 (5-HT(1A) antagonist, 5.6 and 56 mM), 8-OHDPAT (5-HT(1A/7) agonist, 7 and 15 mM), Ketanserin (5-HT(2A) antagonist, 3.7 and 37 mM), or (+/-)-2,5-dimethoxy-4-iodoamphetaminehydrochloride (DOI; 5-HT(2A) agonist, 6.7 and 67 mM) into the LC, followed by a 60-min period of 7% CO(2) exposure. Hypercapnia increased 5-HTIAA levels and 5-HIAA/5-HT ratio within the LC. WAY-100635 and 8-OHDPAT intra-LC decreased the hypercapnic ventilatory response due to a lower tidal volume. Ketanserin increased CO(2) drive to breathing and DOI caused the opposite response, both acting on tidal volume. The current results provide evidence of increased 5-HT release during hypercapnia in the LC and that 5-HT presents an inhibitory modulation of the stimulatory role of LC on hypercapnic ventilatory response, acting through postsynaptic 5-HT(2A) receptors in this nucleus. In addition, hypercapnic responses seem to be also regulated by presynaptic 5-HT(1A) receptors in the LC.
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PMID:Serotonergic mechanisms on breathing modulation in the rat locus coeruleus. 1984 39

Long-term neurochemical changes are responsible for therapeutic actions of fluoxetine. The role of increased central concentration of serotonin by inhibiting its re-uptake via fluoxetine on the central hypercapnic ventilatory response is complex and little is known. We aimed to research the effect of acute intracerebroventricular (ICV) injection of fluoxetine on hypercapnic ventilatory response in the absence of peripheral chemoreceptor impulses and the role of 5-HT2 receptors on responses. Eighteen anesthetized albino rabbits were divided as Fluoxetine and Ketanserin groups. For ICV administration of fluoxetine and ketanserin, a cannula was placed in the left lateral ventricle by the stereotaxic method. Respiratory frequency (fR), tidal volume (V(T)) and ventilation minute volume (V(E)) were recorded in both groups. ICV fluoxetine (10.12 mmol/kg) injection during normoxia caused significant increases in V(T) and V(E) (both P < 0.01) in the fluoxetine group. When the animals were switched to hypercapnia f/min, V(T) and V(E) increased significantly. The increases in percentage values in V(T) and V(E) in Fluoxetine + Hypercapnia phase were higher than those during hypercapnia alone (P < 0.01 and P < 0.05, respectively). On blocking of 5-HT2 receptors by ketanserin (0.25 mmol/kg), the ventilatory response to Fluoxetine was abolished and the degree of increases in V(T) and V(E) in the Ketanserin + Hypercapnia phase were lower than those during hypercapnia alone (P < 0.01 and P < 0.001, respectively). We concluded that acute central fluoxetine increases normoxic ventilation and also augments the stimulatory effect of hypercapnia on respiratory neuronal network by 5-HT2 receptors in the absence of peripheral chemoreceptor impulses.
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PMID:Alterations of central hypercapnic respiratory response induced by acute central administration of serotonin re-uptake inhibitor, fluoxetine. 2213 15