Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ACE-inhibitors have for some time been used in the treatment of hypertension. Apart from inhibiting the conversion of angiotensin I to II, the drugs also affect the metabolism of some inflammatory agents, like bradykinin and substance P. Egg albumin (EA)-sensitized guinea pigs were pretreated with the ACE-inhibitors. Measurement of flare and wheal areas induced by an intradermal injection of EA, showed that enalaprilat significantly increased, whereas cilazaprilat slightly decreased, the reaction area. Enalaprilat also showed an enhancement in histamine and substance P (SP) contents in the skin. In vitro incubation of guinea pig biopsies with enalaprilat potentiated EA- but not SP-induced histamine release. The EA-induced effect was abolished if the animals were pretreated with capsaicin. The conclusion is that cilazaprilat, in contrast to enalaprilat, does not potentiate inflammatory reactions in the guinea pig.
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PMID:Enalaprilat versus cilazaprilat: a comparison of allergic skin reactions in the guinea pig. 171 46

Disturbances in adaptive processes can be induced by chronic exposition to stress or can result from a genetical predisposition. Experimental data of chronically stressed Wistar rats and of spontaneously hypertensive rats (SHR) demonstrate a relation between a decreased level of substance P (SP) in adrenals, the existence of a dependence on endogenous opioid peptides and an increased regulatory level of blood pressure. The endogenous level of SP was determined by using a RIA. The dependence (physical) on endogenous opioid peptides was detected by using the method of "gut dependence". SP injection i.p. once a day for 4 d antagonized the dependence on endogenous opioid peptides and normalized the increased level of blood pressure in both animal models. Investigations on SHR had shown that the adaptive effect of SP on blood pressure and endogenous opioid dependence is bound to the premise of an acute stimulated endogenous opioid system at the moment of SP-application. Experimental findings suggest that different systems of opioid peptides take part in the etiopathogenesis of genetically predisposed hypertension of SHR and in stress-induced increase of blood pressure level of Wistar rats. The effect of SP on blood pressure and endogenous opioid dependence will be discussed as a result of the modulatory influence on the cholinergic-opioid-peptidergic interaction.
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PMID:Endogenous opioid dependence--a basic pathophysiological phenomenon of stress-induced and genetically fixed disturbances in adaptation--influence of substance P. 172 61

In rings of rat portal vein, endothelin-1, endothelin-2, and endothelin-3 caused graded slow contractions and potentiated spontaneous contractions. The apparent EC50 values and maximal responses to 30 nM endothelin were 1.4 nM and 0.96 g for endothelin-1, 5.2 nM and 0.65 g for endothelin-2, and 1.7 nM and 0.62 g for endothelin-3 (n = 4-12). At concentrations producing half the contraction triggered by 80 mM KCl, the order of potencies was endothelin-1 greater than U46619 = angiotensin II greater than bradykinin greater than substance P greater than phenylephrine. Longitudinal portal-mesenteric vein preparations developed very modest contractions to endothelin-1 (0.13 g at 30 nM; n = 5), but their responses to 80 mM KCl and phenylephrine were greater than those of rings. Responses of rings to endothelin-1 were profoundly reduced in Ca(2+)-free medium, but less inhibition was obtained after incubation with nicardipine (up to 1 microM) and/or nickel (up to 0.5 mM), phorbol (up to 0.3 microM), staurosporine (up to 10 nM), or cromakalim (3 microM). Indomethacin (5.6 microM) did not affect responses to endothelin-1. Cromakalim (0.1-3 microM) also relaxed rings constricted with 0.3 nM endothelin-1, and this effect was partially reversed by glibenclamide (3 microM). Thus, endothelins, especially endothelin-1, are potent constrictors of portal vein rings but not of portal-mesenteric vein strips. Their action appears to rely largely on Ca2+ influx from the external medium (only in part via L- and T-type Ca2+ channels) and activation of protein kinase C but not on eicosanoid generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Potent constrictor actions of endothelin-1, endothelin-2, and endothelin-3 in rat isolated portal vein. 173 99

Pain related to fibromyalgia may consist of a complex interaction of nociceptive, neuropathic, dysregulatory central nervous system and psychosomatic mechanisms. Nociceptor pain is based on the excitation of nervous sensors specialized to signal potentially harmful stimuli, i.e., the nociceptors. Metabolic deficiencies in muscle and neurogenic inflammation induced by the release of substance P and other neuropeptides from the peripheral nerve endings may result in chemical sensitization of nociceptors and an ensuing hyperalgesia particularly present in tender points. Neuropathic pain is due to pathological mechanisms within nerve cells and fibers in the peripheral and central nervous system. Pathophysiology may be related to compression (such as in the carpal tunnel syndrome or a vertebral disk herniation) or regeneration of nerves, resulting in ectopic impulse discharges and disturbances of axonal transport. The ensuing neuronal hyperexcitability and trophic changes induced by a disturbed axonal transport system may be major factors of pain in fibromyalgia. Dysregulatory pain denotes pain maintained by dysfunction of efferent control loops. Thus, if spinal motoneuron output results in excessive tension of postural muscle, nociceptors in muscles, tendons and joints might become more excited. Persistent abnormal spinal reflex transmission due to, e.g., peripheral trauma or inappropriate postural habits may result in a vicious circle between muscle hypertension and pain. Similarly, a defective sympathetic control may result in disturbed microcirculation and nociceptor excitation (e.g., in sympathetic algodystrophy). Many symptoms of pain in fibromyalgia (trigger points, pain referral, pain associated with muscle spasm or neurogenic joint immobilization) can be attributed to abnormal control mechanisms in a complex cybernetic system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathophysiological mechanisms of fibromyalgia. 181 May 27

In addition to the classical transmitters noradrenaline and acetylcholine, other transmitters have been identified in perivascular nerves, including 5-hydroxytryptamine, ATP and a number of peptides. This paper discusses pre- and postjunctional neuromodulation of vascular transmission, and cotransmission involving noradrenaline, ATP and neuropeptide Y in sympathetic nerves, acetylcholine and vasoactive intestinal polypeptide in parasympathetic nerves, and substance P, calcitonin gene-related peptide and ATP in 'sensory-motor' nerves. Vasomotor nerves derived from intrinsic neurones, for example in the heart and gut, are also discussed. Subpopulations of endothelial cells store and release a variety of substances, including acetylcholine, substance P, ATP, 5-hydroxytryptamine, vasopressin and angiotensin II, that act on receptors on endothelial cells and lead to the production of endothelium-derived relaxing factor (identified as nitric oxide) which, in turn, produces vasodilation in response to changes in flow and hypoxia. Endothelium-derived contracting factors such as endothelin may also be released. There appears to be a resting dynamic balance between endothelium-derived vasodilator tone and sympathetic vasoconstrictor tone, which is altered under different physiological and pathophysiological circumstances. Long-term (trophic) interactions between perivascular nerves and endothelial cells are discussed, as are the changes in vascular control mechanisms that occur with ageing and hypertension and in the nerves that remain following trauma or surgery.
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PMID:Local mechanisms of blood flow control by perivascular nerves and endothelium. 198 71

The great discovery by Furchgott of the relaxing factor released from the endothelium (EDRF) awakened us to the necessity to reevaluate the functional importance of endothelial cells that have been chemically or physically stimulated. EDRF was first demonstrated to be released by acetylcholine, substance P, bradykinin and calcium ionophore A23187; thereafter, many substances have been found to release EDRF. This factor is quite unstable, is not produced by cyclooxygenase, and is an activator of soluble guanylate cyclase that synthesizes cyclic GMP; its action is suppressed by antioxidants via the superoxide anions produced, potentiated by superoxide dismutase and abolished by methylene blue and oxyhemoglobin. Recently, the role of lipoxygenase products in the production of EDRF was evaluated with new 5-lipoxygenase inhibitors without antioxidant activity. During the last couple of years, the actions and chemical properties of EDRF were verified to be quite similar to those of nitric oxide (NO); therefore, the hypothesis of "EDRF = NO" is widely being accepted. NO is produced from L-arginine via catalysis by an enzyme that is activated by Ca2+. The enzyme activity is inhibited by L-monomethyl arginine and other L-arginine analogs. Chemical and physical stimulations increase intracellular Ca2+ in endothelial cells that seems to be associated with K(+)-channel opening and hyperpolarization. Current interests are directed to the possible roles of NO in the regulation of nerve function. There are evidences suggesting that NO modulates adrenergic nerve function in blood vessels and some brain cell functions regulated by cellular cyclic GMP. Particularly, NO may be a transmitter substance in non-adrenergic, non-cholinergic vasodilator nerves innervating the cerebral arteries. Future investigations will determine the physiological roles of EDRF or NO and its relationships to pathophysiology of vascular dysfunctions, such as vasospasm and those related to hypertension, diabetes, aging, etc., and the extended roles of NO in nerve function, inflammation, immune reactions, etc. would be clarified more extensively by accelerated progress in this field of research.
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PMID:[Endothelium-derived relaxing factor (EDRF)]. 216 93

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.
Hypertension 1990 Apr
PMID:Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats. 218 Aug 19

Angiotensin converting enzyme inhibitors (ACEI) are used widely in the treatment of both hypertension and congestive heart failure. Although usually well tolerated, these medications may produce side effects that may be encountered by the allergist, including cough, angioedema, and rhinitis symptoms. The severity of ACEI-induced cough may vary, and is associated with increased bronchial hyperreactivity in some (but not all) patients as judged by methacholine sensitivity. Angiotensin converting enzyme inhibitor-induced cough may have its onset from one day to 12 months after initiation of therapy, and is not dose dependent. Angioedema caused by ACEI is usually mild and clears with discontinuation of the drug, however cases requiring intubation and tracheostomy have been reported. The mechanism of ACEI-induced cough remains unclear, but could be in part due to accumulation of substances whose degradation may also be impeded by ACEI, such as substance P, bradykinins, and/or prostaglandins. Knowledge of the side effects produced by this class of medication may help patients avoid unnecessary, costly, and often invasive diagnostic evaluations.
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PMID:Angiotensin converting enzyme inhibitors and the allergist. 222 91

If we consider the chemical messengers in the central nervous system, there are about ten classic transmitters--the catecholamines, biogenic amines and amino acids--as opposed to over 50 different neuropeptides. These include previously well-established circulating hormones such as angiotensin, atrial natriuretic peptide, vasopressin and oxytocin, calcitonin and calcitonin gene related peptide (CGRP), the opioid family of peptides, gastrointestinal peptides, pituitary peptides and their releasing factors, and miscellaneous peptides such as the kinins, bombesin, gallanin, and others; all occur as neuropeptides in the brain. There is evidence supporting a role in central cardiovascular control for angiotensin, opioid peptides, substance P, neuropeptide Y, vasopressin, atrial natriuretic peptide, kinins, corticotropin releasing factor, bombesin, somatostatin, and some other peptides. They have been localized in brain areas known to be important for blood pressure regulation, and specific high-affinity peptide receptors have also been discovered. Upon central administration, these peptides produce cardiovascular effects, partly by interacting with other blood pressure-controlling neuroregulators, e.g. catecholamines and GABA. Central inhibition of brain peptide synthesis or interaction with competitive antagonists at the receptor site results in marked cardiovascular effects. Altered peptide levels and activity of synthesizing enzymes, as well as supersensitivity to the pressor action of some brain peptides, have been described in experimental models of hypertension. We are using angiotensin as a model peptide to study the peptidergic control of cardiovascular function.
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PMID:Peptidergic control of cardiovascular function: the angiotensin paradigm. 219 11

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
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PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18


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