Pharmacological Effects of Nicotine on Norepinephrine Metabolism in Rat Brown Adipose Tissue: Relevance to Nicotinic Therapies for Smoking Cessation
| Autor: | Amy B. Jakowski, F. David Tingley, Amy C. Shen, Michael R. Elwell, Steven B. Sands, Jenny Hon Cai, Martin Finkelstein, Dominique Brees |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Nicotine medicine.medical_specialty Toxicology Mediastinal Neoplasms Partial agonist Pathology and Forensic Medicine Rats Sprague-Dawley Norepinephrine (medication) Norepinephrine chemistry.chemical_compound Sex Factors Adipose Tissue Brown Quinoxalines Internal medicine Brown adipose tissue medicine Animals Nicotinic Agonists Neurotransmitter Varenicline Molecular Biology Dose-Response Relationship Drug business.industry Cell Biology Benzazepines Rats medicine.anatomical_structure Endocrinology Nicotinic agonist chemistry Catecholamine Female Smoking Cessation Lipoma business medicine.drug |
| Zdroj: | Toxicologic Pathology. 36:568-575 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | In a two-year carcinogenicity study with administration of high doses of the partial nicotinic agonist varenicline (recently approved for smoking cessation), mediastinal hibernomas occurred in three male rats. To investigate potential mechanisms for partial and full nicotinic agonists to contribute to development of hibernomas, the effects of nicotine on rat brown adipose tissue (BAT) were studied. Male and female rats were administered nicotine at doses of 0, 0.3, and 1 mg/kg subcutaneously for fourteen days. Intrathoracic (mediastinal periaortic and mediastinal perithymic) BAT and interscapular BAT were examined microscopically, and determinations of uncoupling protein-1 (UCP-1) expression and norepinephrine (NE) content were made. Additionally, NE turnover was measured in mediastinal periaortic and perithymic BAT. Nicotine (1 mg/kg) administration resulted in decreased vacuolation only in mediastinal periaortic and mediastinal perithymic BAT of males and elevated UCP-1 in mediastinal periaortic BAT of males and females. Increased NE content occurred only in mediastinal periaortic BAT of males given 0.3 and 1 mg/kg doses, whereas NE turnover was decreased in both males and females given 1 mg/kg. Together, these data demonstrate that nicotine primarily affects mediastinal BAT in male rats, consistent with the gender and location of the hibernomas observed in the two-year carcinogenicity study. |
| Databáze: | OpenAIRE |
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