Catecholamines receptor

Catecholamine receptors are well estabUshed to be altered by a variety of homologous and heterologous influences (104). Thus, in hyperthyroidism, there is an increased level of sympathetic activity associated with increased expression of a- and P-adrenoceptors. 

Waldeck, B., Sensitization by caffeine of central catecholamine receptors, Journal... 

The brain contains many different catecholamine receptors 217 DOPAMINE RECEPTORS 218... 

The catecholamines dopamine, norepinephrine and epinephrine are neurotransmitters and/or hormones in the periphery and in the CNS. Norepinephrine is a neurotransmitter in the brain as well as in postganglionic, sympathetic neurons. Dopamine, the precursor of norepinephrine, has biological activity in the periphery, most particularly in the kidney, and serves as a neurotransmitter in several important pathways in the CNS. Epinephrine, formed by the N-methylation of norepinephrine, is a hormone released from the adrenal gland, and it stimulates catecholamine receptors in a variety of organs. Small amounts of epinephrine are also found in the CNS, particularly in the brainstem. 

The brain contains many different catecholamine receptors. The effects of dopamine are mediated through interaction with five different receptors usually referred to as Drlike (Dj, D5) and D2-like (D2, D3, D4) [33] (Table 12-3). 

TABLE 12-7 Characteristics of catecholamine receptor knockout mice... 

In the case of the P2-catecholamine receptor (illustrated here), the a-subunit of the Gs protein, by binding to adenylate cyclase, leads to the synthesis of the second messenger cAMP. cAMP activates protein kinase A, which in turn activates or inhibits other proteins (2 see p.l20). 

On balance, these actions could support a decrease rather than an increase in the functional state of CNS NE transmission, because depression can be conceptualized as a state of supersensitive catecholamine receptors secondary to decreased NE availability. This reasoning is consistent with the original hypothesis of diminished NE functioning, with antidepressants returning receptors to a more normal state of sensitivity. Siever and Davis ( 41) further elaborated on this concept by suggesting the possibility of dysregulation in the homeostatic mechanisms of one or more neurotransmitter systems, culminating in an unstable or erratic output. 

Early research at our institute found that treatment with lithium decreased the b-adrenergic receptor number, consistent with the noradrenergic down-regulation hypothesis but difficult to reconcile with a complementary theory of mania ( 25). Lithium can also block dopamine receptor supersensitivity, and this is consistent with the postulate that mania is associated with an increased sensitivity of catecholamine receptors. 

Lithium has several effects on the endocrine system. For example, it can interfere with the synthesis and the release of testosterone, leading to an increase in luteinizing hormone levels. The thyroid system has been most implicated in neuroendocrine theories of lithium s antimanic effects. In particular, thyroid hormones can potentiate b-NE activity, and lithium s ability to block their release may subserve its mood-stabilizing properties (i.e., the thyroid-catecholamine receptor hypothesis)... 

Whybrow PC, Prange AJ. A hypothesis of thyroid-catecholamine-receptor interaction its relevance to affective illness. Arch Gen Psychiatry 1981 38 106-113. 

Studies of sudden death in novice as well as experienced drug abusers found that cocaine causes vasoconstriction of the coronary arteries which seems to result from an enhancement of Ca2+ influx across myocardial membranes. However, remember that this class of drug affects other neurotransmitter systems. Cocaine inhbiits reuptake of NE and 5-HT as well as binds to the DA transporter. It increases catecholamine receptor sensitivity but does not seem to directly influence enkephalinergic receptors. In addition it also affects neurotransmission the H, Ach and phenylethylamine pathways. Activation of DA, NE or 5-HT neurons independently does not produce the euphoria associated with cocaine misuse. Euphoria seems to be related to simultaneous inteeraction between catecholamine and serotoninergic systems. 

Orly, J., and Schramm, M. (1976). Coupling of catecholamine receptor from one cell with adenylate-cyclase from another cell by cell-fusion. Proc. Natl. Acad. Sci. USA 73, 4410-4414. 

There are two kinds of catecholamine receptors, the a and fi receptors. The former respond best to norepinephrine, whereas the latter prefer epinephrine. Norepinephrine is normally associated with neurotransmission, and a-adrenergic receptors are indeed found in tissues serviced by the sympathetic nervous system. An example is the smooth muscle, which contracts in response to stimulation by... 

Muscarinic acetylcholine receptors (several t5 es) Catecholamine receptors Serotonin receptors 5-HTj 245 GABAg receptor... 

All three catecholamines are rather polar, due to both the hydroxyl groups and the amino group, which will be mostly protonated at physiological pH. They will thus not cross the blood brain barrier easily, so that in effect the catecholamine pools in the brain and in the periphery will not interfere with each other. Exclusion by the blood brain barrier also applies to many synthetic agonists and antagonists that act on catecholamine receptors, as these compounds often are structurally similar to the physiological mediators. These drugs are useful to influence the peripheral... 

All catecholamine receptors are metabotropic. They act by initiating metabohc processes affecting cellular functions. P-adrenergic receptors, receptors for epinephrine, and norepinephrine act by stimulatory G proteins to increase cAMP in the post-synaptic cell. cAMP binds to and activates protein-kinase enzyme. 

Luttrell, L.M., Ostrowski, J., Cotecchia, S., Kendall, H., and Lefkowitz, R.J. (1993). Antagonism of catecholamine receptor signalling by expression of cytoplasmic domains of the receptors. Science 259, 1453 1457. 

The activation of the stress systems affects all tissues of the organism, and the peripheral immune system is no exception. These effects are mediated through at least tw o pathways via the HPA axis and by virtue of the innervation of lymphatic tissues by autonomic nerve fibers, especially from the sympathetic nervous system. All lymphoid tissues, primary (bone marrow and thymus) as well as secondary (spleen, lymph nodes, and gut-associated lymphoid tissue) are innervated by sympathetic nerve fibers. As discussed above, most lymphoid cells express catecholamine receptors, including B-lymphocytes, CD4- and CD 8-positive T cells, dendritic cells, monocytes, and macrophages. 

The mechanism by which the action of a hormone on its tissue receptor leads to stimulation of adenylate cyclase is not known. Studies concerning the relationship of hormone binding to enzyme stimulation are in their infancy, and there may not be a direct relation between the number of receptors occupied and the extent of enzyme stimulation. The problems involved in the identification of the glucagon [24] and catecholamine receptors [25-27] have been discussed elsewhere. 

Caron MG, Lefkowitz RJ. Catecholamine receptors structure, function, and regulation. Recent Prog Horm Res 1993 48 277-90. 

Evidence accumulated in 1978 for a catecholamine receptor supersensitivity theory of depression. 8 The therapeutic action of antidepressants may be due to delayed post-synaptic changes in receptor sensitivity, rather than to acute events like uptake. Various drugs, including TCA, mianserin, viloxazine and iprindol, as well as electroconvulsive therapy (ECT), but not selective 5-HT uptake inhibitors, caused central alpha-adrenoceptor subsensitivity in rats as measured by noradrenaline (NA)-associated adenylate cyclase or by receptor binding. In vivo, the effects were associated with chronic but not acute treatment, paralleling the clinical effects. MAOI may cause similar effects on chronic but not acute treatment. , 24-27 Brain NA turnover in rats was decreased by chronic desipramine and other TCA, but unaffected by iprindol and increased by mianserin.3,28... 

Catecholamines exert their effects through specific receptors on the target cell surface. However, the effects elicited depend on the type or subtype of receptor with which they interact. There are three types of catecholamine receptor dopamine, a-adrenergic, and )S-adrenergic. Each of these consists of at least two or more subtypes, which differ with respect to ligand affinity, tissue distribution, postreceptor events, and drug antagonists (Table 32-3). 

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