Opiate peptide

Membrane-associated receptors are linked to transducing proteins (like G-proteins) in the inner portion of the membrane. G-protein coupled receptor (GPCR) families comprise a major class of the receptors that are pharmacologically relevant, such as muscarinic acetyl choline receptors, adrenoceptors, dopamine receptors, serotonine, opiate, peptide hormone, purinerg receptors, and also sensory chemoreceptors. A large variety of subtypes are described in the pharmacological literature. 

Watson SJ, Akil H, Richard CW, Barchas JD. (1978). Evidence for two separate opiate peptide neuronal systems. Nature. 275 226-28. 

Endogenous opiate peptides Naloxone precipitates nicotine withdrawal thresholds... 

Opiates and opiate peptides RNH, CF,COiH MeOH-H,0 formic aftylpiienyl Octadecyl or 252... 

Fluorination of the aromatic ring (or in some cases also the introduction of the 18F isotope) in some bioactivc compounds has been successfully performed (e.g., fluoroantipyrine. fluoro-dopa).21 24,35 Regiospecific fluorination of the tyrosine ring of the A-terminal tetrapeptide amide (Tyr — n-Ala — Phe — Gly-NH2) sequence of the opiate peptide dermorphin was achieved in good yield by reaction with acetyl hypofluoritc to give 28.21... 

Methano amino acids 6 and 7 (Scheme 6), which have rigidly defined x1 orientations, have been utilized by several groups and shown to induce y-turn structures. Incorporation of (25,35)-c-Met 7 into the anti-opiate peptide H-Phe-Met-Arg-Phe-NH2 (with replacement of the Met residue) using solid-phase synthesis provided an analogue whose lowest energy conformation involved a y-turn centered around the c-Met residue (Scheme 6)J32 ... 

The demonstration of the existence of strictly defined SARs. which is perhaps Ihe most important criterion of drug action at a specific receptor site, has made possible the most important pharmacologic discoveries. For example, the analgesic actions of morphine and related agents, which are indicative of specific receptors, led to die discovery of endogenous opiate peptides, i.e., the leucine and methionine enkephalins and endorphins. 

Both N-Acetylgalactosaminyltransferase and gal-actosyltransferase activities were suppressed when the cells were pre-treated with opiates or opiate peptides as shown in Table IV. The time course for such studies is obviously crucial and Table V shows an example where the potent opiate fentanyl was used as the inhibitor. It can be seen that the initial inhibition is only observed for 24-48 hrs and that after this time glycosyltransferase levels appear to be normal. 

The reaction was used to prepare many types of biologically interesting derivatives including fluoro hexestrol 29, fluoro tyrosine 30, various 4-fluorosteroidal enones 31, 6-fluorosteroids268, fluorobimans e.g. 32269 and fluorinated opiatic peptides 33, X = F, similar to dermorphin (equation 152)270. 

Yang J (1994) Intrathecal administration of oxytocin-induced analgesia in low-back-pain involving the endogenous opiate peptide system. Spine 19 867-871... 

Because ACTH synthesis originates from the POMC precursor peptide, its production by the pituitary is closely tied to the secretion of endogenous opiate peptides, such as P-endorphin. The physiological effects of endogenous opiates include (1) sedation, (2) an increased threshold of pain, and (3) autonomic regulation of respiration, blood pressure, and heart rate. These peptides are also involved in modifying endocrine responses to stress and water balance... 

Recent studies showed that stress is able to cause an increase in the level of norepinephrine, CRF, ACTH, cortisol (the stress hormones), IL-1, IL-2, and natural killer cells, and an increase in the level of PGE2 (Chavali, et al., 1998 Van Doornrn, et al., 1998). On the other hand, IL-2 induces an increase in CRF, ACTH, and cortisol (Denicoff, et al., 1989 Hanisch, et al 1994, Karanath, et al., 1995). Stress and IL-2 induces an increase of p-endorphin level (the natural painkiller opiate peptide). 

---