Brain opiate receptors

Shavit, Y., Involvement of brain opiate receptors in the immune-suppressive effect of morphine, Proc. Natl. Acad. Sci., 83, 7114, 1986. 

Herkenham M, Pert CB (1982) Light microscopic localization of brain opiate receptors a general autoradiographic method which preserves tissue quality. J. Neuroscl, 2, 1129-1149. 

The actions of all clinically used opiates can now be explained in terms of their acting as agonists at one of the four opiate receptors found in the brain, spinal cord and peripheral nervous system. All four receptors are inhibitory (Table 21.2). 

Heroin (diacetylmorphine) a highly lipophilic drug but has very weak or no affinity for opiate receptors. It penetrates the brain rapidly whereupon it is metabolised to morphine which then binds to the mu receptor. 

O DONAHUE has isolated a naturally occurring peptide from brain that can produce responses similar to PCP when administered to animals. The results are reminiscent of the early studies of the opiopeptides that interact with opiate receptors and produce effects like narcotic drugs when administered to animals. 

Herkenham, M., and Pert, C.B. In vitro autoradiography of opiate receptors in rat brain suggests loci of "opiatergic" pathways. Proc Natl Acad Sci USA 77 5532-5536, 1980. 

Multiple opiate receptors Different regional distribution in the brain and differential binding of opiates and opioid peptides. Mol Pharmacol 16 91-104, 1979. 

OPIATE RECEPTOR SUBTYPES AND BRAIN FUNCTION. Roger M. Brown, Ph.D. Doris H. Clouet, Ph.D. and David P. Friedman, Ph.D., eds. GPO Stock 017-024-01303-0 6... 

H26. Holiday, J. W and Faden, A. I Naloxone acts at central opiate receptors to reverse hypotension, hypothermia, and hypoventilation in spinal shock. Brain Res. 19,295-299 (1980). 

Blume A. Interaction of ligands with the opiate receptors of brain membranes regulation by ions and nucleotides. Proc Natl Acad Sci USA 1978 ... 

The identification of the morphine receptor spurred an effort in many laboratories to find an endogenous agonist for which that receptor was normally intended. Ultimately, a pair of pentapeptides that bound quite tightly to opiate receptors were isolated from mammalian brains. These peptides, called enkephalins (2, 3), show many of the activities of synthetic opiates in isolated organ systems. They do in fact show analgesic activity when injected directly into the brain. It is thought that lack of activity by other routes of administration is due to their rapid inactivation by peptide cleaving enzymes. 

Hammer R. Cocaine alters opiate receptor binding in critical brain reward regions. Synapse. 3 55, 1989. 

Agonist drugs can also bind directly to the postsynaptic receptor, so mimicking the physiological effect of the neurotransmitter for example, morphine and heroin bind to the brain s opiate receptors and, thus, directly stimulate feelings of pleasure and pain... 

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. 

Bodnar RJ, Wiiiiams CL, Lee SJ, Pasternak GW. (1988). Role of mul opiate receptors in supraspinal opiate anaigesia a microinjection study. Brain Res. 447 25-34. 

Lapchak PA, Araujo DM, Collier B. (1989). Regulation of endogenous acetylcholine release from mammalian brain slices by opiate receptors hippocampus, striatum, and cerebral cortex of guinea-pig and rat. Neuroscience. 31(2) 313-25. 

Opiate receptors are linked, via the G-protein system, to K+ ion channels and to voltage-gated Ca " ion channels. Binding of the opiates results in opening of ion channels and hyperpolarisation, so that it is more difficult to initiate an action potential, i.e. they behave like inhibitory neurotransmitters (see above). The binding also results in inhibition of the opening of the Ca ion channels in response to depolarisation. That is, both effects are inhibitory on the nervous activity in the brain, which may explain their analgesic effects. 

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