Subtypes transcriptional regulation

Control of feeding behavior involves peripheral peptides (insulin, ghrelin, leptin) plus several peptides in the CNS (orexins/hypocretins, CCK, galanin, MSH, neuropeptide Y, CRH, cocaine-and-amphetamine-regulated transcript (CART)) [35, 36]. Some of the same peptides are involved in reward systems crucial to drug addiction. Specific receptor blockers are being tested for many of these peptide-receptor systems, with the hope of very selective actins with minimal side effects [35], For example, there are two CCK receptor subtypes, CCK-A and... 

Norepinephrine is released into the synapse from vesicles [(1) in Fig. 2.7] amphetamine facilitates this release. Norepinephrine acts in the CNS at two different types of noradrenergic receptors, the a and the P [see (2a), (2b) and (3) in Fig. 2.7]. a-Adrenergic receptors can be subdivided into receptors (coupled to phospholipase and located postsynaptically) and tt2 receptors (coupled to Gj and located primarily presynapti-cally) (Insel, 1996). P-Adrenergic receptors in the CNS are predominantly of the P subtype (3 in Fig. 2.7). P receptors are coupled to and lead to an increase in cAMP. Cyclic AMP triggers a variety of events mediated by protein kinases, including phosphorylation of the P receptor itself and regulation of gene expression via phosphorylation of transcription factors. 

The multifimctional CaM kinases are collectively referred to as CaM kinases of type II, whereby further subtypes a, p, y and 6 are differentiated. The a and P subtypes of CaM kinase II only occur in the brain whereas the other subtypes are also found in other organs. The multifunctional CaM kinases regulate many processes (see Table 7.1) such as glycogen metabolism, activity of transcription factors, microfilament formation, synaptic release of neurotransmitters from storage vesicles, biosynthesis of neurotransmitters and many more. An important cellular function is assigned to CaM kinase II in brain, where it makes up 0.25 % of the total protein. 

The first identified cannabinoid receptor subtype, CB was cloned and demonstrated to have an amino acid sequence consistent with a tertiary structure typical of the seven transmembrane-spanning proteins that are coupled to G proteins. In addition to being found in the central nervous system, mRNA for CB has also been identified in testes. The central nervous system responses to cannabinoid compounds are believed to be mediated exclusively by CB, inasmuch as CB2 transcripts could not be found in brain tissue by either Northern analysis or in situ hybridization studies. CBj transduces signals in response to central-nervous-system-active constituents of C. sativa as well as synthetic bicyclic and tricyclic cannabinoid analogs, aminoalkylindole, and eicosanoid cannabimimetic compounds. CB is coupled to G, to inhibit adenylate cyclase activity and to a pertussis-sensitive G protein to regulate Ca2+ currents. 

Some of the genes that are commonly regulated by all three arAR subtypes have also been previously identified with traditional methods of detection. Common transcription factors such as c-fos and c-jun (14) as well as the early growth response genes (egr-1) (15) have been found to increase after arAR activation. 

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