Distribution and Retention of Nicotine and Its Metabolite, Cotinine, in the Rat as a Function of Time

Sastry, Rama; Chance, M. B.; Singh, Gurkeerat; Horn, John L.; Janson, V. E.

doi:10.1159/000139274

Cited by 76 publications

(50 citation statements)

References 12 publications

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“…The average plasma nicotine concentration of active smokers is 100 nM to 1 mM (40). The most potent cigarette smoke carcinogens are polycyclic aromatic hydrocarbons and nicotine-specific metabolites such as NNK and NNN (41).…”

Section: Smoking-induced Cancer Formationmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

103

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The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and a-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that a9-nAChR is important for breast cancer formation, and in many in vivo studies, a9-nAChR-specific antagonists (e.g., a-ImI, a-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine-and estrogeninduced breast cancer cell proliferation through inhibition of the a9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation.

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Section: Smoking-induced Cancer Formationmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

103

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“…To this purpose, plasma levels of cotinine-the principal biomarker of nicotine consumption and tobacco exposure-were assessed. Even if there is no general agreement and possible limitations of this measure could be raised (see Discussion), cotinine levels have been reported to be linearly and directly related to daily available nicotine (Rama-Sastry et al 1995;Rosa et al 1992). The rate of body weight gain in these rapidly growing animals was also analyzed.…”

mentioning

confidence: 99%

Peculiar Vulnerability to Nicotine Oral Self-administration in Mice during Early Adolescence

Adriani

Macrı̀

Pacifici

et al. 2002

Neuropsychopharmacology

194

142

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(10 mg/l). After a 6-day period, a fading study was carried out, in which nicotine concentration was reduced to 7 mg/l (days 7-9) and 5 mg/l (days 10-12), to assess whether animals would compensate by increasing their intake from the nicotine solution. In Experiment 2, psychopharmacological effects on locomotion induced by the nicotine solution (0, 10, 30 mg/l) Recent research has emphasized that adolescence is associated with patterns of temporary deviance (Arnett 1992) and the use of various kinds of psychoactive agents (Mathias 1996). Drug abuse in adolescents ranging from 11-12 to 17-18 years of age is likely to start with tobacco smoking, which can be followed by marijuana and/or 1991;Breslau et al. 1993;Nides et al. 1995;Kandel and Chen 2000). Despite the social and scientific importance of deepening our knowledge of this issue (see e.g. Colby et al. 2000), there have been very few investigations on the psychobiological factors contributing to the specific adolescence-related willingness to experience various psychoactive drugs (for a review, see Laviola et al. 1999;Spear 2000). For the purpose of laboratory studies, a suitable animal model of human adolescence is available in rodents. Namely, periadolescence is classically defined as the ontogenetic period that encompasses the week preceding the onset of puberty and the first few days thereafter (Spear and Brake 1983). Periadolescent rodents differ markedly from adults in their spontaneous behavioral repertoire (Cirulli et al. 1996;Terranova et al. 1993;Meaney and Stewart 1981;Panksepp 1981). In fact, elevated levels of novelty seeking and a reduced behavioral and hormonal response to stress (Adriani et al. 1998;Adriani and Laviola 2000) are exhibited by animals around this age. A characteristic hyporesponsivity to the effects of an acute administration of psychostimulants (Spear and Brake 1983;Laviola et al. 1995;Bolanos et al. 1998;Adriani and Laviola 2000), a peculiar pattern of behavioral sensitization following repeated drug exposure (Laviola et al. 1995(Laviola et al. , 2001Adriani et al. 1998), as well as a weak drug-induced place conditioning profile (Adriani et al. 1998;Bolanos et al. 1996Bolanos et al. , 1998 but see Campbell and Spear 2000), are also reported. Based on these findings, an increased vulnerability to the addictive properties of abused drugs has been suggested to be typical of adolescence in both humans and animals models (see Laviola et al. 1999).In the present study, we were interested in nicotine, which beside being the main psychoactive compound implied in tobacco smoking, also shares most of the characteristics of other addictive drugs (Corrigall et al. 1992(Corrigall et al. ,1994Pontieri et al. 1996;Merlo-Pich et al. 1997;Stolerman 1999). Nicotine's effects in mice have been shown to be highly dependent on the genetic background (see Marks et al. 1989;Robinson et al. 1996). However, the interaction between the pharmacological effects and the incentive properties of nicotine during the adolescent period has been largel...

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“…The metabolism of nicotine and other tobacco alkaloids has not been studied in isolated human placenta or placental microsomes where there is no interference from their metabolism in maternal or fetal livers. Of all the metabolites of nicotine described in the literature [6,7,37,38], cotinine has received special attention because (1) its plasma half-life is longer than that of nicotine; (2) its plasma level is useful as a qualitative marker of the use of tobacco products, and (3) its rate of transfer across biological membranes or barriers is slower than that of nicotine. According to present investigations, about 1% of nicotine added to maternal perfusate was metabolized into cotinine and released into maternal and fetal perfusates.…”

Section: Discussionmentioning

confidence: 99%

“…in the authors' laboratory for detection of cotinine in the plasma of smokers and nicotine patch users [26,27]. This HPLC method was modified and adapted to measure nicotine and cotinine in placental perfusates and homogenates.…”

Section: Hplc Methods For the Determination Of Nicotine And Cotinine Imentioning

confidence: 99%

Formation and Retention of Cotinine during Placental Transfer of Nicotine in Human Placental Cotyledon

et al. 1998

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Maternal smoking during pregnancy causes reduction of fetal breathing movements, an effect attributed to nicotine in fetal blood. Nicotine is metabolized to cotinine which has a long plasma half-life and exhibits slow clearance across membrane barriers. It is also known to activate placental phospholipase-A₂-like enzymes, resulting in formation of prostaglandins. Therefore, we studied transport of nicotine in isolated perfused cotyledon of normal human term placenta. The placental cotyledon was perfused with aerated (21% O₂, 5% CO₂) Krebs-Ringer bicarbonate buffer (pH 7.4, 37°C) containing 2% albumin on both maternal (230 ml, 15 ml/min, 35 mm Hg) and fetal (93 ml, 1.75 ml/min, 70 mm Hg) sides in a closed recirculating system. Nicotine (2 mg) was added to the maternal perfusate; perfusate samples (1 ml) were collected from both sides at regular intervals and analyzed for nicotine and cotinine by high-pressure liquid chromatography. This study gave the following results: (1) In about 60–80 min, 18.6% of the nicotine added to the maternal perfusate was transferred to the fetal perfusate, and the maternal/fetal concentration ratio reached 1.0. These results show rapid placental transfer of nicotine, consistent with its high lipid solubility. (2) Less than 1% is metabolized to cotinine in placenta. The ratio of cotinine concentrations in maternal and fetal perfusates reached 1.0 in about 40 min. These studies were also verified using ¹⁴C-nicotine. (3) Maximal reduction in fetal breathing movements occurs at about 30 min, and recovery occurs at 90 min after tobacco smoking by the mother. These observations agree with the rate of placental transfer of nicotine. (4) When nicotine was added on the fetal side, part of it was metabolized to cotinine. However, the maximal concentration of cotinine was twice higher on fetal than on maternal side. These observations suggest that accumulation of cotinine on fetal side may activate prostaglandin formation and trigger spontaneous abortions in pregnant smokers.

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Distribution and Retention of Nicotine and Its Metabolite, Cotinine, in the Rat as a Function of Time

Cited by 76 publications

References 12 publications

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Peculiar Vulnerability to Nicotine Oral Self-administration in Mice during Early Adolescence

Formation and Retention of Cotinine during Placental Transfer of Nicotine in Human Placental Cotyledon

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