Cellular and subcellular localization

a1 - Adrenoceptor subtypes can be differentially distributed in certain tissues. This differential distribution can reflect either expression of receptor protein/message or pharmacological characteristics in functional assays. For example, the predominant a1 -adrenoceptor found in rat spleen is the a1B subtype, and the functional pharmacological profile of a1 -adrenoceptor agonists (i.e. contraction) in this tissue has a1B-adrenoceptor characteristics, as determined by the use of subtype selective antagonists (Aboud et al. 1993; Stam et al. 1998). Although all of the a1 -adrenocetpor subtypes are present in most blood vessels, the pharmacological characteristics of agonist-induced contraction can vary, such that the responses may be a1A (human microvessels, rat caudal artery), a1B (rabbit or canine aorta) or a1D (rat aorta).

The a1-adrenoceptor subtypes are differentially distributed within the central nervous system. Highest levels of a1a-adrenoceptor mRNA are found in regions of the olfactory a1a a1a rffrl

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system, hypothalamic nuclei, and in regions of the brainstem and spinal cord related to motor function (Day et al. 1997). Studies in rat brain have shown a^-adrenoceptor mRNA to be concentrated in cerebral cortex, thalamus, raphe nuclei, cranial, and spinal motorneurons, as well as in the pineal gland. mRNA for the a1d-adrenoceptor is localized to the olfactory bulb, cerebral cortex, hippocampus, dentate gyrus, reticular thalamic nucleus, motor neurons, and the inferior olivary complex. In the thalamus, the a^-and a1d-adrenoceptors have a complimentary distribution (Nicholas etal. 1996). Much less information is available on the distribution of a1-adrenoceptors in the human brain. However, a1-adrenoceptors are found in neocortex and dentate gyrus, although their distribution differs substantially from that observed in the rat (Zilles et al. 1993)

a2-Adrenoceptors are also widely distributed throughout the body. Studies in the rat demonstrate the existence of mRNA for all three a2-adrenoceptor subtypes in the central nervous system. a2a-Adrenoceptor mRNA is most widely distributed, being found in the cerebral cortex, locus coeruleus, amygdala, hypothalamic paraventricular nucleus, nucleus tractus solitarii, ventrolateral reticular formation, spinal cord, and dorsal root ganglia. Message for the a2b-adrenoceptor is found almost exclusively in the thalamus. The a2c-adrenoceptor is found in olfactory bulb, islands of Calleja, cerebral and cerebellar cortex, hippocampal formation and dorsal root ganglia (Nicholas et al. 1996). In human brain, radioligand binding assays demonstrate the presence of a2A-adrenoceptor protein in frontal cortex, cerebellum, and hippocampal formation, with another subtype (a2B or a2o) predominant in neostriatum (Grijabla etal. 1996).

In rat brain, mRNA for the p1-adrenoceptor is widely distributed with radioligand assays using dissected rat brain showing that p1-adrenoceptors are typically associated with fore-brain structures (cerebral cortex, striatum, and hippocampus), In contrast, message for the ^-adrenoceptor is concentrated in olfactory bulb, hippocampal formation, piriform cortex, and cerebellar cortex (Nicholas et al. 1996) with densest binding in the cerebellum (Nicholas et al. 1996). Interestingly, it has been suggested that the (-adrenoceptors of rat cerebral cortex are localized primarily on glial cells (Strong et al. 1991). The (3-adrenoceptor does not appear to be present in the central nervous system.

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