Endogenous peptide effect

A synthetic form of the endogenous peptide brain natriuretic peptide (BNP) has recently been approved for use in acute cardiac failure as nesiritide. This recombinant product increases cGMP in smooth muscle cells and effectively reduces venous and arteriolar tone in experimental preparations. It also causes diuresis. The peptide has a short half-life of about 18 minutes and is administered as a bolus intravenous dose followed by continuous infusion. Excessive hypotension is the most common adverse effect. Measurement of endogenous BNP has been proposed as a diagnostic test because plasma concentrations rise in most patients with heart failure. 

The opioid alkaloids are classic examples of non-peptide ligands that have later been discovered to be mimetics of endogenous peptides. For example, morphine 5 (Figure 1.4.3) imitates the effect of flexible peptides, for example Met-enkephalin 4, at the common recognition site of the receptor for both compounds... 

Many endogenous peptides and proteins are released in a pulsatile fashion and subject to complex feedback control mechanisms, consequentially, drag timing plays a crucial role in determining the observed effect. 

Since the ratio between therapeutic effect and adverse effects varies among opioids, great effort has been made to synthesize compounds with a better ratio of antinociceptive activity versus adverse side effects. This effort to discover better, safer compounds necessitated the development of laboratory methods that are sensitive to and, therefore, could be used to quantify the adverse effects of opioids. Moreover, the discovery of several distinct types of receptors that can interact with opioids or with endogenous peptides... 

Neurotensin is an endogenous peptide neurotransmitter inducing a variety of effects, including analgesia, hypothermia, and increased locomotor activity. It is also involved in regulation of dopamine pathways. Neurotensin is found in endocrine cells of the small intestine, where it leads to secretion and smooth muscle contraction (Moore and Black, 1991). 

ATRIAL NATRIURETIC PEPTIDE RECEPTOR AGONISTS include ANP itself (also called atrial natriuretic factor (ANF), or atrlopeptin), a peptide made up of 28 amino acids and is contained in secretory granules in heart atrial cells. ANP is released in response to stretch in the atria, as occurs with increased central venous pressure, thus signalling volume overload in the circulation. The peptide has an effect on the kidney leading to increased Na and water excretion, vasodilation, increased vascular permeability and modified release of a number of other hormones and neurotransmitters. There are at least three related endogenous peptides ANP (atrial natriuretic peptide),... 

There are several examples of peptidomic studies using iTRAQ labeling. One study identified substrates of prolyl peptidases in mouse models, and another explored the effect of diurnal variation on the endogenous peptide composition of human parotid saliva (64,65). 

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