Electrophysiological and biochemical responses of mouse vomeronasal receptor cells to urine-derived compounds: possible mechanism of action.
Receptor cells of the vomeronasal organ (VNO) are thought to detect pheromone-like molecules important for reproductive physiology. Several compounds derived from male mouse urine have been demonstrated to affect endocrine events in female mice. In the present study, the ability of these compounds to affect VNO activity was tested. In dissociated VNO cells held under voltage clamp conditions, application of dehydro-exo-brevicomin (DHB) evoked an outward current at negative holding potentials and an inward current at positive holding potentials. Under current clamp, DHB reduced action potential firing. Since DHB application caused a decrease in membrane conductance, this compound appeared to act by reducing inward current through closing an ion channel. Biochemical experiments tested the effects of DHB and 2-(sec-butyl)-4,5-dihydrothiazole (SBT) on cAMP levels in the VNO. A mixture of DHB and SBT decreased cAMP levels in VNO sensory tissue and had no effect on VNO non-sensory tissue. The results suggest that pheromones have an inhibitory influence on action potential generation and on cAMP levels in receptor cells of the VNO.
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235, USA. rmoss@mednet.swmed.edu
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Moss
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Flynn
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Shen
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Dudley
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Novotny
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000652:urine; D004594:Electrophysiology; D005260:Female; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010675:Pheromones / Q000494:pharmacology* / Q000652:urine; D011506:Proteins / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology / Q000652:urine; D019147:Vomeronasal Organ / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure
D019086:Bridged Bicyclo Compounds, Heterocyclic; D010675:Pheromones; D011506:Proteins; D013844:Thiazoles; C035737:major urinary proteins; C049351:2-(sec-butyl)-4,5-dihydrothiazole; C040729:3,4-dehydrobrevicomin; C074535:2,3-dehydrobrevicomin