Distribution of Nicotine in the Central Nervous System

Schmiterlöw, Carl G.; Hansson, Emma; Andersson, Gustav; Appelgren, Lars‐Erik; Hoffmann, Philip C.

doi:10.1111/j.1749-6632.1967.tb13708.x

Cited by 72 publications

(22 citation statements)

References 7 publications

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“…These investigators suggested that the high nicotine concentration ratio resulted from some factor other than the pH gradient, for example, selective dissolution in non-aqueous components (reflecting its lipid solubility) or selective intracellular binding. Neither seems very likely in ganglia, because (a) autoradiographs have shown that nicotine tends to be excluded from, rather than concentrated in, such lipid elements as myelin (Schmiterlow, Hansson, Andersson, Appelgren & Hoffmann, 1967;Brown et al, 1969a) and (b) the uptake of nicotine by ganglion cells is proportional to the external concentration over a wide concentration range, which argues against a finite number of binding sites (Brown et al, 1971). …”

Section: Uptake Of 3h-nicotinementioning

confidence: 99%

Intracellular pH in rat isolated superior cervical ganglia in relation to nicotine‐depolarization and nicotine‐uptake

Brown

Halliwell

1972

British J Pharmacology

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Summary1. The intracellular pH (pHi) of rat isolated superior cervical ganglia incubated in normal Krebs solution (pH,=7-37) was estimated to be 7-33 from the uptake of a weak acid, 14C-5,5-dimethyloxazolidine-2,4-dione (DM0). Addition of 30 ,uM nicotine for 30 min reduced the DMO-estimated pHi by 015 units to 7'18. This effect was prevented by hexamethonium (25 mM) or by depolarizing the ganglion with K+ (124 mM).2. 3H-Nicotine (30 pAM) was concentrated within the ganglia to an intracellular/extracellular concentration ratio (CI/C0) of 5'54 in normal Krebs solution and 4'61 in 2 5 mm hexamethonium. This would suggest an intracellular pH of 6&54 and 6'63 respectively. In ganglia previously depolarized by K+ the corresponding values for Ci/C0 were 4'02 (minus hexamethonium, estimated pHi 6'95) and 4417 (plus hexamethonium, estimated pHK 6'94).3. A multicompartment cell interior comprising an acid cytoplasm (pH-6'6) and more alkaline nucleus and mitochondria is proposed to explain the difference between the values of pHi estimated from the uptake of DMO and nicotine. It is suggested that the fall in pH, during nicotine-depolarization results from metabolic stimulation following Na+ entry.

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Section: Uptake Of 3h-nicotinementioning

confidence: 99%

Intracellular pH in rat isolated superior cervical ganglia in relation to nicotine‐depolarization and nicotine‐uptake

Brown

Halliwell

1972

British J Pharmacology

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“…Uptake is lowered in vivo by pentobarbital anesthesia, and is reduced in brain slices by lowering temperature. 16 -22 " 27 Most of the 3 H in the brain at 240 sec is associated with 3 H-nicotine; less than 3% is due to 3 H-cotinine, a metabolic derivative of 3 H-nicotine that is produced in liver and kidney and appears in blood about 180 sec after an intravenous injection, but is poorly permeable at the blood-brain barrier. 26 -…”

Section: Mathematical Analysis Of Datamentioning

confidence: 99%

“…4 -34~36 If 3 H-nicotine binding by brain is a measure of density of cells and nerve endings, then short-term experiments (50 sec or less) with nicotine might be used to estimate LCBF and longterm experiments (5 min or more) to estimate density of cells and nerve endings. 16 -22~27 Nicotine, when incorporating the positron emitter 13 N, might also be used in man to measure regional blood flow by means of emission computed tomography.…”

Section: Smentioning

confidence: 99%

“…In this paper, we compare LCBF's that were obtained with each of 3 tracersu C-antipyrine, 14 Ciodoantipyrine and 3 H-nicotine -in regions of the rat brain that were dissected out according to criteria of Glowinski and Iversen 13 and Chiueh et al 14 Knowledge of LCBF in these specific regions is required to calculate regional cerebrovascular permeability to a variety of agents. 16 The mathematical treatment of Kety 5 was employed to estimate LCBF with both 14 C-antipyrine and 14 C-iodoantipyrine. The treatment could not be used with 3 H-nicotine, however, because this tracer binds to brain and is not freely exchangeable between brain and blood.…”

Section: Lcbf In Conscious Raj/ohno Et Almentioning

confidence: 99%

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Local cerebral blood flow in the conscious rat as measured with 14C-antipyrine, 14C-iodoantipyrine and 3H-nicotine.

Ohno¹,

Pettigrew²,

Rapoport³

1979

Stroke

108

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“…The pharma cokinetics of nicotine have been widely stud ied in humans [1-6], Its plasma half-time is approximately 2 h in humans. The lipoid sol ubility of nicotine and its penetration of the blood-brain barrier [7], its distribution in the central nervous system [8], its distribution kinetics [9]. and its metabolism in liver [10] and lung [11] have also been studied in exper imental animals.…”

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confidence: 99%

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

Sastry¹,

Chance²,

Singh

et al. 1995

Pharmacology

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Nicotine is oxidized to its major metabolite, cotinine, which has a long biological half-life (19–24 h). The plasma concentration of cotinine has been used as an index of tobacco smoke exposure. Cotinine possibly increases the turnover rate of platelet-activating factor (PAF) because it is a potent activator of PAF hydrolase, and it may play a significant role in tobacco-induced arterial thrombosis. Therefore, we studied the distribution and retention of nicotine as it was metabolized to cotinine in the rat. Nicotine (1 mg/kg, 5 µCi/kg) was administered into the femoral vein of male Sprague-Dawley rats under nembutal anesthesia. At different times (5–60 min) after nicotine administration, nicotine and its metabolite, cotinine, were determined by HPLC in plasma, liver, kidney, heart and brain. Within 5–10 min after administration, nicotine concentrations reached peak values in plasma (2,160 pmol/ml) and the organs analyzed. The plasma level of nicotine decreased by 50% within 20 min (half-time) after its intravenous administration. The half-time of nicotine in the brain was about 50 min. The half-times of nicotine for the other organs were about 20–25 min. The major metabolite, cotinine, accumulated in plasma, and by about 30 min the concentrations of nicotine and cotinine in plasma were about equal (890–1,000 pmol/ml). While cotinine accumulated in plasma, nicotine was eliminated by the kidney. While the nicotine concentrations decreased with time in all organs, cotinine concentrations remained constant. These observations indicate that nicotine is renally eliminated or metabolized to cotinine while cotinine exhibits a long retention time and accumulates in plasma. This plasma accumulation may contribute to activation of PAF turnover rate and to thrombosis.

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Distribution of Nicotine in the Central Nervous System

Cited by 72 publications

References 7 publications

Intracellular pH in rat isolated superior cervical ganglia in relation to nicotine‐depolarization and nicotine‐uptake

Intracellular pH in rat isolated superior cervical ganglia in relation to nicotine‐depolarization and nicotine‐uptake

Local cerebral blood flow in the conscious rat as measured with 14C-antipyrine, 14C-iodoantipyrine and 3H-nicotine.

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

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