Dependence Desensitisation

Inhaled nicotine is efficiently delivered to the brain (see chapter by Benowitz, this volume) where it selectively interacts with its central targets, the neuronal nicotinic acetylcholine receptors (nAChRs). The multiple subtypes of uAChR (see chapter by Collins et al, this volume) all bind nicotine but with different affinities, depending on the subunit composition of the uAChR. Binding may result in activation or desensitisation of uAChRs, reflecting the temporal characteristics of nicotine dehvery and local concentration of nicotine. Another level of complexity of the actions of nicotine reflects the widespread and non-uniform distribution of uAChR subtypes within the brain, such that nicotine can influence many centrally regulated functions in addition to the reward systems. In this chapter, we address the consequences of nicotine interactions with nAChRs at the molecular, cellular and anatomical levels. We critically evaluate experimental approaches, with respect to their relevance to human smoking, and contrast the acute and chronic effects of nicotine. 

Liang M, Eason MG, Jewell-Motz EA et al (1998) Phosphorylation and functional desensitisation of the a2A-adrenergic receptor by protein kinase C. Mol Pharmacol 54 44-9 Lim W, Kim SJ, Yan HD et al (1997) Ca2+-channel dependent and -independent inhibition of exocytosis by extracellular ATP in voltage-clamped rat adrenal chromaffin cells. Pflugers Arch 435 34 12... 

Depending on the severity of his symptoms the patient can be referred to his GP for allergy testing with a view to desensitisation injections once the allergen has been identified. Mr JA should be advised to start his hay fever treatment four weeks before the start of the season, depending on which pollen type he is allergic to. 

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