Receptors morphinic

Figure 7.3. Agonists used by Martin and coworkers (5, 6) to define k and cr receptors. Morphine (1) was the prototypical ligand used to characterize ja receptors.

Morphine, as we have already discussed, is an alkaloid which relieves pain and acts in the CNS. There are two conclusions which can be drawn from this. The first is that there must be analgesic receptors in the CNS. The second conclusion is that there must be chemicals produced in the body which interact with these receptors. Morphine itself is not produced by humans and therefore the body must be using a different chemical as its natural painkiller. 

Proteins Opiate receptors Morphine, nalbuphin, nalaxone... 

Morphine is a naturally occmring alkaloid from the opium poppy seed. Modern formulations employ synthetic morphine. Major and minor sites of morphine activity include spinal and supraspinal opioid receptors. Morphine binds to and activates mu, kappa and delta receptor subtypes. 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Opiates iateract with three principal classes of opioid GPCRs )J.-selective for the endorphiQS,5-selective for enkephalins, and K-selective for dynorphias (51). AU. three receptors have been cloned. Each inhibits adenylate cyclase, can activate potassium channels, and inhibit A/-type calcium channels. The classical opiates, morphine and its antagonists naloxone (144) and naltrexone (145), have moderate selectivity for the. -receptor. Pharmacological evidence suggests that there are two subtypes of the. -receptor and three subtypes each of the 5- and K-receptor. An s-opiate receptor may also exist. 

Dynorphin may also influence nociception at the spinal level. The levels of prodynorphin mRNA and immunoreactive dynorphin increase in the chronic inflammatory arthritic model (158). Dynorphin also inhibits morphine or P-endorphin-induced analgesia in naive animals and enhances analgesia in tolerant animals, indicating that this peptide may have a regulatory role in opioid analgesia (159). This effect does not appear to be mediated by a classical opioid receptor, since des-tyrosine dynorphin, which does not bind to opioid receptors, also antagonizes morphine analgesia (160). 

Narcotic analgesic. A drug that alleviates pain by interacting with the morphine receptor. 

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