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Role of nitric oxide in the anticonvulsive effect of progesterone
Affiliation:1. Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina;2. Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA;3. Biomedicine Research Institute of Buenos Aires, Partner Institute of the Max Planck Society (MPSP), National Research Council, Ciudad Autónoma de Buenos Aires (CABA), Buenos Aires, Argentina;4. Laboratory of Molecular Endocrinology, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina;1. Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China;2. Department of Laparoscope, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China;3. Department of Gastrointestinal surgery, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China;4. Department of Surgical Oncology, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China;5. Department of Endoscopy, Third Affiliated Hospital of Second Military Medical University, Shanghai 200438, China;6. Department of Urology surgery, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China;7. Department of Ultrasound, Huashan Hospital Affiliated to Fudan University, Shanghai, China;8. Department of Hepatic Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai 200438, China;9. Department of Breast and Thyroid surgery, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China;1. Department of Urology surgery, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China;2. Department of Rehabilitation Medicine, First Affiliated Hospital of Second Military Medical University, Shanghai, 200433, China;3. Department of Breast and Thyroid surgery, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China;4. Department of Internal Medicine, The No. 313 Hospital of PLA, Huludao 125000, China;5. Department of Internal Medicine, First Affiliated Hospital of JinZhou Medical University, JinZhou 121001, China;6. Department of Gastroenterology, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China;1. AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Bondy, France;2. Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France;3. APHP, Jean Verdier Hospital, Biochemistry Department, Bondy, France;4. Clinical Research Unit, Lariboisière-St Louis, Fernand Widal Hospital, APHP, Paris, France
Abstract:Described here is an investigation of the potential interaction of the nitric oxide signaling pathway with the anticonvulsant effects of progesterone. In ovariectomized Swiss mice, the threshold for seizures induced by intravenous infusion of pentylenetetrazole was determined after treatment with progesterone (25, 50, or 75 mg/kg, given subcutaneously 6 h before seizure testing) or vehicle. Progesterone induced significant anticonvulsive activity at moderate (50 mg/kg) and high (75 mg/kg) doses. This effect of progesterone was abolished by the NO precursor compound l-arginine (200 mg/kg). Moreover, when subeffective doses of progesterone (25 mg/kg) and the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (10 mg/kg) were injected, a strong anticonvulsant effect was observed. These findings suggest a potential role for NO signaling as an anticonvulsant target in females.
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