Neuropeptide, vasodilator

Whittle, B.J.R. (1990). Role of endothelium-derived vasodilator, nitric oxide and neuropeptides in gastric integrity. Gastroenterology 98, A147. 

Peptides are used by most tissues for cell-to-cell communication. As noted in Chapters 6 and 21, they play important roles in the autonomic and central nervous systems. Several peptides exert important direct effects on vascular and other smooth muscles. These peptides include vasoconstrictors (angiotensin II, vasopressin, endothelins, neuropeptide Y, and urotensin) and vasodilators (bradykinin and related kinins, natriuretic peptides, vasoactive intestinal peptide, substance P, neurotensin, calcitonin gene-related peptide, and adrenomedullin). This chapter focuses on the smooth muscle actions of the peptides. 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

Calcitonin gene-related peptide aCGRP is a 37-amino acid neuropeptide that was first identified in 1982 as an extremely potent vasodilator (Amara et al., 1982). It is... 

The stimulation of C fibers by capsaicin causes a subset of sensory airway neurons to release several neuropeptides, which include tachykinin, substance P and neurokinin A. In addition to capsaicin, other endogenous mediators including histamine, prostaglandins and bradykinins can also result in their release. These neuropeptides are responsible for neurogenic inflammation, which is characterized by vasodilation, mucus secretion, plasma protein extravasation, increased expression of the adhesion molecules and bronchoconstriction. 

Besides neuropeptides, nitric oxide is an inflammatory mediator in the airways, which is also a vasodilator and a neurotransmitter. Nitric oxide is produced by the enzymatic action of nitric oxide synthetase on L-arginine. Airways contain this enzyme in three different forms, two of which termed neuronal and endothelial nitric oxide synthetase are constitutive whereas the third form called inducible nitric oxide synthetase is inducible. The inflammatory cytokines including IL-1 and TNF-a augment the expression of inducible nitric oxide synthetase in human airway epithelial cells. Nitric oxide causes bronchodilation as a result of the relaxation of bronchial smooth muscles. It has also been suggested that nitric oxide is the neurotransmitter of the inhibitory NANC bronchodilation. The detrimental effects of nitric oxide include airway inflammation and vasodilation. It causes airway edema by increasing the erudition of plasma due to increased blood flow to postcapillary venules. The increased blood flow may also contribute to an increased mucus secretion. The role of nitric oxide in inflammatory responses has not yet been established. 

Neuropeptide Y produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, and respiratory depression. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional actions include inhibition of transmitter release from sympathetic and parasympathetic nerves vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

The etiology of migraine headaches is currently attributed to the neurovascular hypothesis, with the release of vasoactive neuropeptides and subsequent vasodilation of blood vessels. Serotonin plays an important role in migraine pathophysiology, and serotonin agonists have an important role in migraine treatment. 

Sublimaze fentanyl. substance K neurokinin A neuropeptide K. substance P (SP) is a naturally occurring 11 amino acid residue C-terminally amidated peptide, and is a tachykinin present in the brain of vertebrate species, in spinal ganglia and in the intestines. It is formed from the precursor preprotachykinin A (PPT-A). It acts as a tachykinin RECEPTOR AGONIST and Stimulates extravascular smooth muscle, is a powerful VASODILATOR and transient HYPOTENSIVE, and causes salivation and increased capillary permeability. Notably, Af-terminally deleted fragments (e.g. SP(4-11)) are as active as substance P itself on many systems. It is used as a pharmacological tool. 

In addition to stimulating afferent nerve fibre endings in mucosal surfaces and producing a typical PCSI effect, OC also induces the release of tachykinins or neuropeptides like substance P and neurokinin A. This induces neurogenic inflammation of the airway blood vessels, epithelial cells, glands and smooth muscle, leading to vasodilation, increased vascular permeability, neutrophil chemotaxis, mucus secretion and bronchospasm (Smith and Stopford, 1999). 

Cetirizine competitively antagonizes histamine at the Hi-receptor site and is indicated in the symptomatic relief of symptoms (e.g., nasal, nonnasal) associated with seasonal and perennial allergic rhinitis treatment of uncomplicated skin manifestations of chronic idiopathic urticaria. Histamine is a potent vasodilator, bronchial smooth-muscle constrictor, and stimnlant of nociceptive itch nerves. In addition to histamine, mnltiple chemical itch mediators can act as pruritogens on C-fibers, including neuropeptides, prostaglandins, serotonin, acetylcholine, and bradykinin. Furthermore, new receptor systems such as vanilloid, opioid, and canna-binoid receptors on cutaneous sensory nerve fibers that may modulate itch offer novel targets for antipruritic therapy. 

Histamine is a potent vasodilator, bronchial smooth muscle constrictor, and stimulant of nociceptive itch nerves. In addition to histamine, multiple chemical itch mediators can act as pruritogens on C-fibers, including neuropeptides, prostaglandins, serotonin, acetylcholine, and bradykinin. 

Mammalian tachykinins, a family of tachykinin peptides traditionally classified as neurotransmitters that include substance P (SP), neurokinins (NKA and NKB), two elongated versions of NKA, neuropeptide y (NP,) and neuropeptide K (NPK), hemokinin 1 (HK-1) and endokinins A-D. They act as neurotransmitters, paracrine or endocrine factors, neuroimmunomodulators, and have also immune and pro-inflammatory actions. Furthermore, mammalian tachykinins are involved in vasodilation, plasma extravasation, smooth muscle contraction, secretion, neural excitation, and processing of sensory information. The biological actions are mediated via three known mammalian tachykinin receptors, NKi, NK2, and NK3 [N. M. Page et al, Proc. Natl. Acad. Sci. USA 2003, 100, 6245 N. M. Page, Peptides 2005, 26, 1356 L. Liu, E. Burcher, Peptides 2005, 26, 1369]. 

The mechanism of this interaction is not understood. It has been proposed that tacrolimus may act on the same biochemical pathway as alcohol potentiating a capsaicin-mediated release of neuropeptides, which increase vasodilatory effects. Alternatively, cutaneous aldehyde dehydrogenase inhibition in areas where tacrolimus has been applied may increase cutaneous aldehyde levels that, through prostaglandins as mediators, could lead to vasodilation following alcohol consumption. - ... 

The biological actions of capsaicin are primarily attributable to release of the neuropeptide substance P, calcitonin gene-related peptide (CGRP), and neurokinin A from sensory neurons. These transmitters from primary sensory neurons communicate witir other cell types. They produce alterations in the airway mucosa and neurogenic inflammation of the respiratory epithelium, airway blood vessels, glands, and smooth muscle. Alterations in multiple effector organs lead to bronchoconstriction, increased vascular permeability, edema of the tracheobronchial mucosa, elevated mucosal secretion, and neutrophil chemotaxis (Tominack and Spyker, 1987). Capsaicin-induced effects of bronchoconstriction, vasodilation, and plasma protein extravasation are mediated by substance P. In addition, substance P can cause bronchoconstriction through stimulation of c-fibers in pulmonary and bronchial circulation. 

Parasympathetic activity results in vasodilation and increased blood flow to the nose, while sympathetic nerves cause vasoconstriction and decreased blood flow. However, the classical view, which assigned opposing actions to the sympathetic and parasympathetic systems on their target tissues, has given way to the current view of complex interactions between classical neurotransmitters (acetylchoUne and norepinephrine), neuropeptides, target cells, and soluble mediators released by the target cells. The actions of parasympathetic fibers are mediated by acetylcholine, VIP, and NO. Norepinephrine and neuropeptide Y (NPY) are released from sympathetic efferents. NPY is a potent vasoconstrictor of nasal capacitance vessels (36), and it increases the expression of adhesion molecules (37). 

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