Their Receptors in HAD

Neuroprotective and Neurotoxic Ejfects of Chemokines and Their Receptors in HAD 

In contrast to HTV-1 coreceptors, some chemokine ligands have the ability to reduce or ablate neuron toxicity. High levels of chemokines RANTES, MIP-la, and others have been shown to reduce neuron death (Meucci et al., 1998 Kaul and Lipton, 1999), while SDF-1, at higher concentrations may actually promote neuronal death (Hesselgesser et al., 1998 Kaul and Lipton, 1999 Zheng et al., 1999b). The mechanism is not yet completely understood, but may rely upon simple competitive inhibition, receptor expression changes on the cell surface, or other unknown mechanisms. 

Therapeutic Avenues Directed Toward Chemokines and Their Receptors 

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For the last forty years, many reports have emerged on the hormone-like effects of chemical compounds such as pesticides and industrial chemicals upon wildlife and humans. The effects of these materials are believed to be either direct or indirect. Direct effects involve positive or negative interactions with the hormone receptors. Indirect effects may result when the synthesis of hormones or their receptors is altered, or the transport, metabolism, or elimination of hormones is modified in some way. The discovery of hormone-like properties of some compounds was made long after their release into the environment. It was shown soon after their introduction that aviation crop dusters handling DDT had low sperm counts and workers at a plant producing the insecticide kepone were reported to have low libido, sperm counts and to be impotent. Subsequently, experiments conducted in laboratory animals demonstrated unambiguously the oestrogenic activity of these pesticides. 9 refs. 

The selective serotonin reuptake inhibitors (SSRIs) represent a chemically diverse class of agents that have as their primary action the inhibition of the serotonin transporter (SERT) (Figure 30-3). Fluoxetine was introduced in the United States in 1988 and quickly became one of the most commonly prescribed medications in medical practice. The development of fluoxetine emerged out of the search for chemicals that had high affinity for monoamine receptors but lacked the affinity for histamine, acetylcholine, and adrenoceptors that is seen with the tricyclic antidepressants (TCAs). There are currently six available SSRIs, and they are the most common antidepressants in clinical use. In addition to their use in major depression, SSRIs have indications in GAD, PTSD, OCD, panic disorder, PMDD, and bulimia. Fluoxetine, sertraline, and citalopram exist as isomers and are formulated in the racemic forms, whereas paroxetine and fluvoxamine are not optically active. Escitalopram is the S enantiomer of citalopram. As with all antidepressants,... 

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