Brain receptor sites

Zukin, S.R., and Zukin, R.S. Identification and characterization of 3H phencyclidine binding to specific brain receptor sites. In Domino, E.F., ed. PCP (phencvli di ne) Hi stori cal and... 

By late evening the LSD had left those brain receptor sites, and Hofmann was able to sleep. Sadly, Hofmann said nothing about his dreams, but did note that sleep completely cured his psychosis. When he awakened,... 

Hydrazone derivatives 258 of oxymorphone, naloxone, and naltrexone have been made by reaction with anhydrous hydrazine and designated oxymor-phazone (170), naloxazone (171), and naltrexazone (172). All three hydrazones exhibited a high binding affinity for in vitro rat brain receptor sites. 

This structural feature appears to be crucial for the binding to brain receptor sites responsible for neurotransmitter action at certain nerve terminals. Such amines can affect a wide variety of behavior, from controlling appetite and muscular activity to creating potentially addictive euphoric stimulation. 

The original monoamine hypothesis of depression states that depressions are associated with a deficiency of catecholamines, particularly norepinephrine, at functionally important adrenergic receptor sites in the brain. Elation conversely may be associated with an excess of such amines. The hypothesis was articulated in 1966 only after the mechanism of action of the tricyclic antidepressant desipramine and of the psychostimulants... 

After initial experiments demonstrating that the antiserum was capable of completely inhibiting the binding of [ H]PbTx-3 to its receptor site in rat brain membranes (Figure 9), we began studies designed to evaluate potential of the antiserum for prophylaxis and treatment of brevetoxin intoxication (34). The tethered rat model was used, and surgical implantations were identical to those described above. Heart rate, core and peripheral body temperatures, lead VIO ECG, and arterial blood pressure were monitored continuously. Respiratory rate was recorded each 5 min for the first 3 hr, then each 15 min until 6 hr. 

Figure 9. Anti-PbTx antiserum inhibition of [ H]PbTx-3 binding to its receptor site in rat brain membrane preparations. Labeled toxin (0.5 nM in 1 ml PBS) was incubated with rat brain membranes (125 fig total protein) and increasing amounts of anti-PbTx antiserum (- -) or pre-immune serum (- -) for 1 hr at 4 C. Membrane-bound radioactivity was then measured in a centrifugation assay as previously described (8),...

TABLE 1. Drug inhibition of specific binding of various 3H-ligands to sigma and PCP receptor sites in brain... 

Cardinah, D. P. Vacas, M. I. (1980), Molecular endocrinology of melatonin Receptor sites in brain and peripheral organs. Adv. Biosci. 29, 237-46. 

Landwehrmeyer B., Mengod G., Palacios J. Differential visualization of dopamine D2 and D3 receptor sites in the rat brain. A comparative study using in situ hybridization histochemistry and ligand binding autoradiography. Eur. J. Neurosci. 5 145, 1993. 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

Research into the properties of opiates has provided more insights into the processes that make up psychopharmacological actions than any other class of drug this is because opiates bind to receptor sites that are affected by endorphins - the brain s indigenous opiates. These endorphins are implicated in pain thresholds, natural highs and our capacity for addiction to opiates. 

If opiates are such addictive and potentially lethal compounds, why does the body respond to them As with the cannabinoids (Chapter 7), it has been discovered that the body and brain possess numerous opiate-specific receptor sites. As many as nine receptor subtypes have been identified, with three of them being the most important p (mu), k (kappa) and 8 (delta). The finding that the distribution of opiate receptors did not parallel the distribution of any known neurotransmitter prompted the search for and identification of a number of endogenous compounds specific to these receptors. These enkephalins and endorphins are manufactured within the brain and other body systems (especially the gut and intestines) and form the body s natural response to pain. They appear to be produced in bulk chains of amino acids called polypeptides , with each active neurotransmitter being composed of around five amino acid molecules. These active neurotransmitters are subsequently cleaved from the larger polypeptides at times of demand for example, it has been demonstrated that the plasma levels of these active compounds rise during childbirth, traumatic incidents and vigorous physical exercise. 

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