Cholinergic receptors distribution

Elgoyhen AB, Vetter DE, Katz E, RotWinCV, Heinemann SF, Boulter J (2001) alO a determinant of nicotinic cholinergic receptor function in mammalian vestibular and chochlear mechanosen-sory hair cells. Proc Natl Acad Sci 98 3501-3506 Fabian-Fine R, Skehel P, Erington ML, Davies HA, Sher E, Stewart MG, Fine A (2001) Ultra-structural distribution of the a7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci 21 7993-8003... 

Figure 2.15 illustrates the distribution of the main cholinergic receptors in the human brain. 

Mechanism of Action A smoking deterrent that inhibits acetylcholine at the auto-nomicganglia. Blocks central nicotinic cholinergic receptors, which inhibits effects of nicotine. Therapeutic Effect Reduces blood pressure decreases desire to smoke. Pharmacokinetics Completely absorbed following PO administration. Widely distributed. Excreted in urine. Half-life 24 hr. 

The limited distribution of the H+, K+-ATPase, which is found mainly in the tubulovesicular and canalicular membranes of the gastric parietal cell. This is in contrast to, for example, the more widely distributed H2 and cholinergic receptors. 

Muscarinic Cholinergic Receptor Binding Regional Distribution In Monkey Brain. Brain Res. 66 541 546. 

Muscarinic cholinergic receptor binding regional distribution in monkey brain Brain Res. 66, 541-546 ... 

Spencer DG Jr, Horvath E, Traber I. 1986. Direct autoradiographic determination of Ml and M2 muscarinic acetylcholine receptor distribution in the rat brain Relation to cholinergic nuclei and projections. Brain Res 380 59-68. 

A major drawback of many studies of the chemical neuroanatomy is that they were conducted in only one species, the rat. There is extensive evidence for species differences in the distribution of the synthetizing enzyme of acetylcholine (ChAT), muscarinic cholinergic receptors and acetylcholinesterase (see Section 3.10.), and there is reason to assume that a similar interspecies variability exists for other transmitter systems. The expression of Zebrin by certain subpopulations of Purkinje cells, and the zonal patterns in the distribution of 5 -nucleotidase, only occur in certain species. It is a fortunate coincidence for the experimental neuroscientist that the Zebrin zonal pattern is expressed in rats, but in other species like the cat or macaque monkeys all Purkinje cells are Zebrin-immunoreactive. Many species-differences in the chemical neuroanatomy of the cerebellum may be due to the selectivity of the antibodies employed in the im-munocytochemical techniques, but other differences may be real and may reflect true variations in structure or in the transmission and second messenger systems of the cerebellum. 

Neustadt A, Frostholm A, Rotter A (1988) Topographical distribution of muscarinic cholinergic receptors in the cerebellar cortex of the mouse, rat, guinea pig, and rabbit A species comparison. J. Comp. Neurol, 272, 317-330. 

D. (1989) Distribution of cholinergic receptors in the rat and human neocortex. In M. Frotscher and U. Misgeld (Eds.), Central Cholinergic Synapse, Vol. 57, pp. 212-228, Bikhauser Verlag, Boston. 

Acetylcholine (ACh) and cholinergic receptors were considered in some detail in Chapter 8. Table 12-3 illustrates the distribution of ACh in the (rat) brain. Cells in various parts of the brain are sensitive to ACh applications. In the cat the microapplication of ACh in the cerebral cortex causes a response in a significant fraction of neurons. 

In addition, cholinergic receptors are distributed extensively in the CNS and participate in diversified functions such as audition, vision, learning and memory, ingestive behaviors (thirst and hunger), thermoregulation, locomotor activity, diurnal rhythms, sleep, and sexual activity. 

Species differ quantitatively and qualitatively in their response to anti-ChEs, This is evident in variable doses that cause death in 50% of a test population (LD50) (Table 1) as well as the levels that yield no effect (NOEL), no adverse effect (NOAEL), the lowest level an effect is observed (LOEL), and the lowest level an adverse effect is observed (LOAEL). To adequately compare OP effects across species, the route and duration of exposure should be similar since absorption and distribution are influenced by the route of administration. These are key factors in determining the body burden of the compound. Moreover, similar end points must be compared across spede.s [e.g, LDjg, the effective dose for 50% (ED50) AChE inhibition in blood or brain, cholinergic receptor binding, or behavioral tests]. 

In experiments in ferret lungs, Barnes et al. showed that 3-receptors were located near airway smooth muscle and their numbers increased in the smaller airways. They also found that a large number of these receptors was present in the alveoli (22). In other experiments, they found an increase in both a- and P-receptors in peripheral airways and a decrease in cholinergic receptors (23). These investigators have also shown that a similar distribution pattern for P-receptors is found in the human lung (Table 6) (24). 

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