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Fluoxetine inhibits arginine vasopressin (AVP)‐stimulated water permeability in rat inner medullary collecting duct (IMCD) via alpha‐2 mechanism
Author(s) -
Rouch Al,
Kudo Lucia
Publication year - 2006
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.20.5.a1221-a
Subject(s) - fluoxetine , vasopressin , endocrinology , chemistry , medicine , pharmacology , serotonin , biology , receptor
Fluoxetine is widely used as an anti‐depressant drug that inhibits reuptake of serotonin. The drug also induces hyponatremia by an unknown mechanism. Evidence shows that fluoxetine does not promote the release of vasopressin that would lead to hyponatremia ( Marar IE and Amico JA, Endocrine, 8: 13–18, 1998 ). Effects of fluoxetine on renal physiology are not known. The purpose of this study was to determine if fluoxetine affects water permeability in the IMCD. Terminal IMCDs from male Wistar rats were isolated and perfused via standard methods. To measure osmotic water permeability (P f , μm/sec), bath fluid was hypertonic to luminal fluid (545 vs 300 mOsm/Kg H 2 O). Agents were added to the bath – AVP at 220 pM and fluoxetine at 2.5 μM. In one set of experiments (n=4), fluoxetine reduced AVP‐stimulated P f from 1235±135 to 587±220 (p<.01). This inhibitory effect was reversible. In another protocol (n=5) fluoxetine failed to affect basal P f (29±9). Subsequent addition of AVP increased P f to 93±18 and the removal of fluoxetine raised P f to 591±200 (p<.01). Fluoxetine failed to decrease P f stimulated by the nonhydrolyzable cAMP analog 8‐chlorophenylthio cAMP (n=4). To investigate the inhibitory mechanism, we used the selective alpha‐2 antagonist atipamezole. In this protocol (n=4) atipamezole reversed the fluoxetine‐induced inhibition of AVP‐stimulated P f from 235±92 to 657±153 (p<05). We conclude that fluoxetine inhibits AVP‐stimulated Pf in rat IMCD via a pre‐cAMP‐dependent mechanism mediated by alpha‐2 adrenoceptors. The mechanism for fluoxetine‐induced hyponatremia remains unknown.