Catecholamines uptake

Coyle, J.T. and Snyder, S.H., Catecholamine uptake by synaptosomes in homogenates of rat brain stereospecificity in different areas, J. Pharmacol. Exp. Then, 170, 221, 1969. 

Poddar, M.K. and Dewey, W.L., Effects of cannabinoids on catecholamine uptake and release in hypothalamic and striatal synaptosomes, J. Pharmacol. Exp. Ther., 214, 63, 1980. 

Reith M., Kramer H., Sershen H., Lajtha A. Cocaine completely inhibits catecholamine uptake into brain synaptic vesicles. Res. Commun. Subst. Abuse. 10 205, 1989. 

Drugs that block the catecholamine uptake process (e.g., cocaine, tricyclic antidepressants, and phenothiazines) are apt to block the anti hypertensive action of which of the following drugs ... 

Prazosin, terazosin, and doxazosin are selective cq-receptor blockers that inhibit catecholamine uptake in smooth muscle cells of the peripheral vasculature, resulting in vasodilation. 

Chang-Tsui YYH, Ho IK. 1980. Effect of Kepone (chlordecone) on synaptosomal catecholamine uptake in the mouse. Neurotoxicology 1(3) 643-651. 

On the other hand, theophylline inhibits reverse uptake catecholamine uptake, which can elevate the level of cychc adenosine monophosphate, thus causing a broncholytic effect. Finally, theophylline is an adenosine receptor blocker, and this may be responsible for its broncholytic effect. 

A.S. Horn, S.H. Snyder, Steric requirements for catecholamine uptake by rat brain synaptosomes, studies with rigid analogues of amphetamine, J. Pharmacol. Exp. Ther. 180 (1972) 523-530. 

Synthesis inhibitors block tryptophan hydroxylase, the first rate-determining enzyme in serotonin synthesis. Although p-chlorophenylalanine (4.111) can decrease serotonin levels by more than 90%, this agent does not cause the sedation that is seen after catecholamine depletion with reserpine. Therefore, reserpine, although capable of depleting 5-HT vesicles, causes sedation by a catecholaminergic mechanism that inhibits uptake-2. It acts on the membrane of the synaptic vesicle and seems to prevent 5-HT and catecholamine uptake into the granule. 

Because neuronal uptake is necessary for the hypotensive activity of guanethidine, drugs that block the catecholamine uptake process or displace amines from the nerve terminal (see Chapter 6) block its effects. These include cocaine, amphetamine, tricyclic antidepressants, phenothiazines, and phenoxybenzamine. 

Pemoline, an oxizolidine compound, acts similarly to methylphenidate—through catecholamine uptake inhibition in the CNS (27) with minimal sympathomimetic effects (57). Although pemoline is not the first-line stimulant for the treatment of ADHD, it has been successfully used for the treatment of this disorder in both children and adults (28,30). Pemoline has also been used for the treatment of daytime sleepiness associated with narcolepsy (31), and although it is somewhat effective for this purpose (33), it is not a first-line choice owing to its potentially lethal liver toxicity. 

A particularly devastating substance that affects neurotransmission is the illicit drug cocaine, which blocks catecholamine uptake at nerve terminals. Addictive cocaine is particularly dangerous because it can cross the blood-brain barrier readily. 

Kimelberg HK (1986) Occurrence and functional significance of serotonin and catecholamine uptake by astrocytes. Biochem Pharmacol 35 2273-2281. 

Nichols, J. W., and Deamer, D. W. (1990), Catecholamine uptake and concentration of liposomes maintaining pH gradients, Biochim. Biophys. Acta, 455, 269-278. 

Mazei MS, Pluto CP, Kirkbride B, Pehek EA. Effect of catecholamine uptake blockers in the caudate-putamen and sub-regions of the medical prefrontal cortex of the rat Brain Res 2002 936 58-67. 

Donnan GA, Kaczmarczyk SJ, Paxinos G, Chilco PJ, Kalnins RM, Woodhouse DG, Mendelsohn FA (1991) Distribution of catecholamine uptake sites in human brain as determined by quantitative [3H] mazindol autoradiography. J Comp Neurol 304 419-434 Eisenhofer G (2(X)1) The role of neuronal tmd extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol Ther 91 35-62... 

Ahnert-Hilger G, Nurnberg B, ExnerT et o/. The heterotrimeric G-protein Guo2 inhibits catecholamine uptake into secretory granules. In revision... 

Catecholamine uptake is driven by the pH gradient across the vesicle membrane (Schuldiner eta/., 1979). 

Table 1. Catecholamine uptake into permeabilized PC 12 cells... 

The mechanism of the central action of amphetamine continues to be explored and the prevailing evidence points to multiple mechanisms involving catecholamine release, inhibition of catecholamine uptake, MAO inhibition and a direct intrinsic action73-75. Dependence on amphetamine and other stimulant drugs, its clinical manifestations and treatment are the subject of two excellent reviews76,77. 

Schwaiger, M., Hutchins, G.D., Kalff, V., Rosenspire, K., Haka, M.S., Mallette, S., Deeb, G.M., Abrams, G.D., Wieland, D., 1991. Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography. J. Clin. Invest. 87, 1681-1690. 

Dopexamine (Dopacard) is a synthetic analog related to dopamine with intrinsic activity at dopamine Dj and D2 receptors as well as at P2 receptors it may have other effects such as inhibition of catecholamine uptake. It appears to have favorable hemodynamic actions in patients with severe CHF, sepsis, and shock. In patients with low cardiac output, dopexamine infusion significantly increases stroke volume with a decrease in systemic vascnlar resistance Tachycardia and hypotension can occnr, bnt nsnally only at high infusion rates. 

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