Opiate hormones peptide

Because of drug-monitoring programs in clinical chemistry, many IA methods have been developed for opiates, steroid hormones, peptide hormones, CNS drugs, drugs of abuse, and drugs with a narrow therapeutic window. Many IA methods have been developed recently for endogenous biochemical markers. Only a few of these are included in the table as illustration. It would be impossible to cover so many biochemical markers in this space. 

The BZ stmcture also has provided a molecular scaffold for a number of peptide receptor ligands (26). Antagonists for the cholecystokinin (CCK-A) receptor, eg, devazepide (65), the thyrotropin-releasing hormone (TRH) receptor, eg, midazolam (66), and the /i -opiate receptor, eg, tifluadom (67), as well as a series of ras famyl transferase inhibitors, eg, BZA-2B (68) (30) have been identified (Table 4). 

At the time of the discovery of Met-enkephalin, its sequence was observed to be identical to that of residues 61—65 contained in the C-fragment of the pituitary hormone p-Hpotropin [12584-99-5] (p-LPH) (see Hormones), first isolated in 1964 (11). In 1976, the isolation of a larger peptide fragment, P-endorphin [60617-12-1] that also displayed opiate-like activity was reported (12). This peptide s 31-amino-acid sequence comprised residues 61—91 of P-LPH. Subsequentiy, another potent opioid peptide, dynorphin [72957-38-17, was isolated from pituitary (13). The first five amino acids (qv) of this 17-amino-acid peptide are identical to the Leu-enkephalin sequence (see Table 1). 

In the trans Golgi compartment the peptide is sorted via secretory vesicles into a regulated pathway. In contrast to vesicles of the constitutive pathway, vesicles of the regulated pathway are stored in the cytoplasm until their stimulated release. Membrane depolarisation as well as a wide range of substances such as intracellular mediators, neuropeptides, neurotransmitters, classical hormones, cytokines, growth factors, ions and nutrients induce somatostatin secretion. General inhibitors of somatostatin release are opiates, GABA, leptin and TGF- 3. 

Amino acid receptors Monoamine receptors Lipid receptors Purine receptors Neuropeptide receptors Peptide hormone receptors Chemokine receptors Glycoprotein receptors Protease receptors Metabotropic glutamate and GABAb receptors Adrenoceptors, dopamine and 5-HT receptors, muscarinic and histamine receptors Prostaglandin, thromboxane and PAF receptors Adenosine and ATP (P2Y) receptors Neuropeptide Y, opiate, cholecystokinin VIP, etc. Angiotensin, bradykinin, glucagon, calcitonin, parathyroid, etc. Interleukin-8 TSH, LH/FSH, chorionic gonadotropin, etc. Thrombin... 

Fragments of the peptide hormone p-lipotropin have been found to show similar binding to opiate receptors. These molecules, the endorphins, show profound CNS activity in experimental animals. It is of interest that one of these, p-endorphin, incorporates in its chain the exact sequence of amino acids that constitutes methionine enkaphalin. 

FIGURE 1 8-5 Tissue-specific processing of the pro-opiomelanocortin (POMC) precursor yields a wide array of bioactive peptide products. Processing of the POMC precursor varies in various tissues. In anterior pituitary, adrenocorticotropic hormone (ACTH (1-39)) and P-1 ipo tropin (P-LPH) are the primary products of post-translational processing. Arcuate neurons produce the potent opiate P-endorphin (P-endo (1-31)) as well as ACTIK1 -13) NIT,. Intermediate pituitary produces a-melanocyte-stimulating hormone (aMSH), acetylated P endof 1 31) and P-endo(l-27). NTS, nucleus tractus solitarius. 

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. 

The present review will focus on the behavioral consequences of two peptidergic compounds, oxytocin and vasopressin. A variety of other peptides, such as corticotropin releasing hormone (CRH), gonadotropin-hormone releasing hormone (GNRH), and the endogenous opiates, such as beta-endorphin (to name only a few) also influence behavior. 

Neuronal projections from the hypothalamus to other regions of the brain relay important output information that influence blood pressure, appetite, thirst, circadian rhythm, behavior, nociception (pain perception), and others factors. Although many of these neurons release neurotransmitter amines at synapses, some of them are known to release neurotransmitter peptides. These include, among others, peptides that closely resemble hormones formed in the gastrointestinal system as well as the endogenous opiates (Table 31-3). 

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). 

There are many small oligopeptides that serve as neurotransmitters and hormones. The enkephalins, endorphins, etc. have already ben mentioned in the section on opiate receptors. Two amino acids that serve in this way are glycine, an inhibitory transmitter, and glutamic acid, an excitatory transmitter. gamma-Aminobutyric acid (GABA) is less well established, but probably an inhibitory transmitter. Peptide hormones like vasopressin and somatostatin are made in the pituitary gland or hypothalamus and influence processes elsewhere in the body. 

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