Further transformation led to total synthesis of morphine
of total synthesis of morphine from starting materials such as ..
Although granule cells contain the vast majority of dynorphin-immunoreactivity found in the hippocampus, the specific site of dynorphin release was not determined. Release either from recurrent collaterals or from dendrites of the granule cells is possible. Functionally, as the postsynaptic cell is the source of a molecule acting on the presynaptic terminal, dynorphin is acting as a retrograde transmitter. This inhibitory modulation of synaptic transmission mediated by dynorphin may be important in the pathophysiology of the hippocampus, because kappa opioids have been shown to be neuroprotective in excitotoxicity studies. In this role, endogenously released dynorphin could be acting in a compensatory manner to limit hyperexcitability existing during seizure activity. Consistent with this hypothesis is the phenomena of mossy fiber sprouting which occurs in human temporal lobe epilepsies. Contrary to expectations, the time course of this proliferation of mossy fiber recurrent collaterals into the inner molecular layer following a kindling paradigm could not be correlated with an increase in granule cell excitability. Rather, a recovery of inhibition was seen, which is consistent with the inhibitory influence of dynorphin as we have described above. Thus endogenous dynorphin modulation of synaptic activity in the dentate gyrus region may have a prominent role in the pathological and physiological function of the hippocampus.
Numerous studies have described opioid-mediated actions on induction in the two opioid-containing pathways in the hippocampal formation. Although discrepancies among reports have occurred, it can be noted once again that endogenous opioid actions are correlated with high-frequency stimulation events. If one assumes that the phenomena of is representative of learning and/or memory mechanisms, then by analogy with their interactions with endogenous opioids should potentially affect these processes as well.
Endorphin - definition of endorphin by The Free Dictionary
Morphine is one of the 40 alkaloids present in opium from Papaver somniferum, and is one of the strongest known analgesic compounds . Endogenous morphine has been characterized in numerous mammalian cells and tissues , , , and its structure is identical to that of morphine from poppy (for review see , ). In mammals, the biosynthesis of endogenous morphine is associated with that of dopamine and catecholamines , , , , , . Morphine biosynthesis was recently shown in the SH-SY5Y human neuronal catecholamine-producing cell line , , a well-known model for studying neuronal secretion , . Recently, our group has reported the presence of morphine-6-glucuronide (M6G), previously considered a product of morphine catabolism, in the secretory granules and secreted material of bovine adrenal chromaffin cells. In these cells, M6G represents the final product of endogenous alkaloid biosynthesis and is formed through the action of an UDP-glucuronosyltransferase 2B-like enzyme (UGT2B). In chromaffin granules, M6G is bound to the intragranular phosphatidylethanolamine-binding protein (PEBP or Raf kinase inhibitor protein) , which also binds morphine . Secretion of M6G, catecholamines, and PEBP into the blood is likely to occur during stress situations, and could be involved in different stress-modulating or pain-modulating mechanisms via binding to µ opioid receptors (MORs), which are present on numerous cell types , , . Together, all these observations suggest that endogenous alkaloids may represent new neuroendocrine factors .