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Serotonergic neurotransmission in the locus coeruleus modulates hypercapnic ventilatory response
Author(s) -
Gargaglioni Luciane H,
SouzaMoreno Vanessa,
Szawka Raphael E,
AlselmoFranci Janete A.,
Bícego Kenia C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.621.7
Subject(s) - ketanserin , hypercapnia , serotonergic , locus coeruleus , serotonin , chemistry , microinjection , agonist , 5 ht receptor , endocrinology , tidal volume , medicine , raphe , receptor , respiratory system , central nervous system
We assessed the possible modulation of respiratory response to hypercapnia by serotonin (5‐HT), through 5‐HT 1A and 5‐HT 2 receptors, in the locus coeruleus (LC). 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 was measured before and after microinjection of WAY‐100635 (5‐HT 1A antagonist, 5.57 e 55.7 mM in 100nL), Ketanserin (5‐HT 2 antagonist, 3.66 e 36.6 Mm in 100nL) or DOI (5‐HT 2 agonist, 69.9 mM in 100nL) into the LC, followed by a 60‐min period of 7%CO 2 exposure. Hypercapnia increased 5‐HTIAA levels and 5‐HT turnover (5‐HIAA/5‐HT) within the LC. WAY‐100635 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. In addition, 5‐HT presents opposite effects on CO 2 ‐ drive to breathing depending on the receptor that it binds in the LC: whereas activation of the 5‐HT 1A receptors stimulates hypercapnic ventilatory response, activation of the 5‐HT 2 inhibits it. Supported by FAPESP and CNPq.