Cotinine Overcome the Decrease of Prostacyclin Formation Induced by Nicotine after Sympathetic Stimulation in Microsomes from Isolated Rabbit Heart
نویسندگان
چکیده
Article history: Received on: 08/03/2013 Revised on: 04/04/2013 Accepted on: 14/06/2013 Available online: 30/06/2013 We studied the effects of cotinine, the major metabolite of nicotine, on nicotine-induced decrease in prostacyclin (PGI2) synthase activity of microsomes from isolated rabbit heart after sympathetic stimulation. Rabbit hearts were isolated along with their sympathetic nerves and perfused in accordance to the Langendorff method. Hearts were randomly divided into 10 groups treated with cotinine, either during sympathetic stimulation or prior to nicotine administration. PGI2 formation in cardiac microsomes was assessed by radioimmunoassay. The results showed that sympathetic stimulation increased PGI2 synthase activity of heart microsomes by 32 %. Nicotine dose dependently decreased PGI2 while cotinine increased it. In addition, perfused before nicotine, cotinine prevented the PGI2 decreasing effect of nicotine. The results suggest that pre-treatment with cotinine can be involved in the modulation of nicotine effects on PGI2 in hearts subjected to sympathetic stimulation.
منابع مشابه
Microsomal N-glucuronidation of nicotine and cotinine: human hepatic interindividual, human intertissue, and interspecies hepatic variation.
Two of the abundant conjugates of human nicotine metabolism result from the N-glucuronidation of S-(-)-nicotine and S-(-)-cotinine, transformations we recently demonstrated in liver microsomes. We further studied these microsomal N-glucuronidation reactions with respect to human hepatic interindividual, human intertissue, and interspecies hepatic variation. The reactivities of microsomes from h...
متن کاملThe Effect of Chronic Inflammation on Knee Joint Vascular β-adrenoceptors in Rabbit
It has been shown that inflammation reduces the effectiveness of sympathetic nerves in the regulation of knee joint blood flow, and the joint vascular- ß adrenoceptors are changed due to acute inflammation from a majority of ß-1 to an equality of ß-1 and ß-2 receptors.. To investigate the role of sympathetic nerves in nerve induced vasoconstriction and changes in joint vascular ß-adrenoceptors ...
متن کاملGlucuronidation of nicotine and cotinine by UGT2B10: loss of function by the UGT2B10 Codon 67 (Asp>Tyr) polymorphism.
Nicotine, the major addicting agent in tobacco and tobacco smoke, undergoes a complex metabolic pathway, with approximately 22% of nicotine urinary metabolites in the form of phase II N-glucuronidated compounds. Recent studies have shown that UGT2B10 is a major enzyme involved in the N-glucuronidation of several tobacco-specific nitrosamines. In the present study, microsomes of UGT2B10-overexpr...
متن کاملN-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases.
Nicotine is considered the major addictive agent in tobacco. Tobacco users extensively metabolize nicotine to cotinine. Both nicotine and cotinine undergo N-glucuronidation. Human liver microsomes have been shown to catalyze the formation of these N-glucuronides. However, which UDP-glucuronosyltransferases contribute to this catalysis has not been identified. To identify these enzymes, we initi...
متن کاملN-glucuronidation of nicotine and cotinine in human: formation of cotinine glucuronide in liver microsomes and lack of catalysis by 10 examined UDP-glucuronosyltransferases.
Two predominant human glucuronide metabolites of nicotine result from pyridine nitrogen atom conjugation. The present objectives included determination of the kinetics of formation of S(-)-cotinine N1-glucuronide in pooled human liver microsomes and investigation of the UDP-glucuronosyltransferases (UGTs) involved in N-glucuronidation of nicotine isomers and S(-)-cotinine by use of recombinant ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2013