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)

The occurrence and distribution of peptide-containing nerve fibers to the cerebral circulation are described. Immunocytochemical studies have revealed that cerebral blood vessels are invested with nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). In addition, there are studies reporting the occurrence of putative neurotransmitters such as cholecystokinin, dynorphin B, galanin, gastrin releasing peptide, vasopressin, neurotensin, and somatostatin. The nerves occur as a longitudinally oriented network around large cerebral arteries. There is often a richer supply of nerve fibers around arteries than veins. The origin of these nerve fibers has been studied by retrograde tracing and denervation experiments. These techniques, in combination with immunocytochemistry, have revealed a rather extensive innervation pattern. Several ganglia, such as the superior cervical ganglion, the sphenopalatine ganglion, the otic ganglion, and small local ganglia at the base of the skull, contribute to the innervation. Sensory fibers seem to derive from the trigeminal ganglion, the jugular-nodose ganglionic complex, and from dorsal root ganglia at level C2. The noradrenergic and most of the NPY fibers derive from the superior cervical ganglion. A minor population of the NPY-containing fibers contains VIP instead of NA and emanates from the sphenopalatine ganglion. The cholinergic and the VIP-containing fibers derive from the sphenopalatine ganglion, the otic ganglion, and from small local ganglia at the base of the skull. Most of the SP-, NKA-, and CGRP-containing fibers derive from the trigeminal ganglion. Minor contributions may emanate from the jugular-nodose ganglionic complex and from the spinal dorsal root ganglia. NPY is a potent vasoconstrictor in vitro and in situ. VIP, PHI, SP, NKA, and CGRP act via different mechanisms to induce cerebrovascular dilatation. The sympathetic, the parasympathetic, and the sensory systems appear to be involved in modulating cerebrovascular tone in hypertension and in conditions of threatening vasoconstriction, e.g., subarachnoid hemorrhage and migraine.
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PMID:Neuropeptides in the cerebral circulation. 270 77

Experiments were performed on isolated human cerebral arteries to evaluate the role desensitization and tachyphylaxis might play in preventing certain agonists from producing prolonged vasoconstriction after subarachnoid hemorrhage. In addition, the antiproteases leupeptin and pepstatin were studied to ascertain whether these peptides might inhibit contraction as does antithrombin III. The maximal contraction to KCl was used as a standard for comparing the responses elicited by the agonists, the decay of the responses to the agonists over 15 minutes was used as an index of desensitization, and the percentage of decrease in response to a second application of the agonist over the first was a measure of tachyphylaxis. The results showed that desensitization and tachyphylaxis greatly reduced or abolished the contractile responses to norepinephrine, serotonin, angiotensin II, arginine vasopressin, substance P, neuropeptide Y, neurotensin, thrombin, uridine triphosphate, linoleic acid, melittin, and cathepsin D. Moreover, some arteries failed to respond to some of these agonists, and no contractile response was elicited by acetylcholine or bradykinin. In contrast, prostaglandins E2, D2, and F2 alpha, as well as plasmin, produced sustained contractions, without tachyphylaxis, but only prostaglandin E2 and plasmin produced contractions at concentrations of 10(-7) M or less that were comparable to those of KCl. None of the antiprotease peptides inhibited the responses to KCl whereas small concentrations (6 X 10(-8) M) of antithrombin III did. The results support the hypotheses that the phenomenon of desensitization and tachyphylaxis would prevent many diverse agents from acting as spasmogens and that substances like antithrombin III present in the cerebrospinal fluid after hemorrhage could immediately protect patients from cerebral vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacodynamic evaluation of human cerebral arteries in the genesis of vasospasm. 368 86

The authors have studied the changes induced by subarachnoid hemorrhage (SAH) in the density and distribution of cerebral perivascular nerves in monkeys and rats. The SAH was induced in monkeys by placement of an autologous blood clot after opening the basal cisterns over the arteries of the circle of Willis on one side. In the rat study, SAH was induced by injection of autologous arterial blood into the cisterna magna. The nerves examined were adrenergic nerves, acetylcholinesterase (AChE)-containing nerves, vasoactive intestinal polypeptide (VIP)-like immunoreactive nerves, and substance P-like immunoreactive nerves. In the monkey study, all animals underwent baseline cerebral angiography, then had repeat angiography just before sacrifice on Day 2, 7, 28, or 70 after SAH. Two sham-operated monkeys underwent the surgical procedure without clot placement and were sacrificed on postoperative Day 7, after repeat angiography. Clot placement in monkeys reduced staining of all middle cerebral artery (MCA) perivascular nerves for between 2 and 28 days post-SAH. The number of stained nerve fibers of MCA's on the non-operated side was slightly reduced on Days 2 and 7 after SAH. Sham-operated monkeys showed a mild reduction of staining in all nerves, but only on the operated side. Cerebral vasospasm was observed on all angiograms taken on Days 2 and 7 following SAH. No vasospasm was found in normal or sham-operated monkeys. The disappearance of nerve staining without associated vasospasm was found on the operated side of the sham-operated monkeys and on the clot side of the animal sacrificed on Day 28 after SAH. Rats sacrificed on Days 2 and 7 post-SAH showed reduction in adrenergic and VIP-like immunoreactive staining around basilar arteries, while nerves containing AChE were not affected. Saline-injected rats exhibited no change in the appearance of perivascular innervation. These results suggest that SAH as well as surgical manipulation of the vessel wall caused a reduction of the studied substances in cerebral perivascular nerves. This reduction in immunoreactive staining of perivascular nerves did not correlate with the development of angiographic vasospasm after SAH.
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PMID:Cerebral perivascular nerves in subarachnoid hemorrhage. A histochemical and immunohistochemical study. 376 Sep 64

Cerebrovascular changes after intrathecal (ith) administration of gammaglobulins against substance P (SP) or calcitonin gene-related peptide (CGRP) were investigated before and following a simulated subarachnoid haemorrhage (SAH) in the squirrel monkey. The SAH was produced by injection of homologous blood into the interpeduncular fossa and the cisterna magna. The gammaglobulins were given both prior to the blood injections and daily in 5 days post-SAH. The effect of the gammaglobulins was examined by angiography pre-SAH and at 10 min and at 6 days post-SAH, i.e. the time points for maximal acute and late spasm in the present model. Cerebral blood flow (CBF) was measured under general anesthesia at day 6 post-SAH with an autoradiographic technique. Five of nine animals treated with CGRP antigammaglobulin died from respiratory failure. Four animals received SP antigammaglobulin and two control animals received normal globulin. SP antigammaglobulin per se had no effect on baseline arterial diameter, while CGRP antigammaglobulin significantly reduced the diameter of the arteries. SP antigammaglobulin prevented the occurrence of acute spasm and significantly reduced the degree of late spasm. Moreover, the reduction in CBF noted in the control SAH animals was significantly reduced. In contrast, CGRP antigammaglobulin treatment had no effect on the degree of spasm and did not cause any change in CBF as compared to controls. The finding that CGRP but not SP antigammaglobulin significantly reduces the arterial diameter in conjunction with our previous demonstration that a post-, but not preganglionic trigeminal lesion reduces the baseline arterial diameter, indicates that CGRP could be the transmitter involved in a peripheral axon reflex. The function of SP might be as a neurotransmitter conveying information to the brainstem. The transmitter role is supported by the effect of SP antigammaglobulin impairing SP containing neurons and, in that way, mimicking a bilateral trigeminal rhizotomy.
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PMID:Cerebrovascular changes following administration of gammaglobulins against substance P or calcitonin gene related peptide in monkey with subarachnoid haemorrhage. 750 91

While the presence of a robust perivascular neural network accompanying cerebral and dural blood vessels that contain various neuropeptides is well documented, the functional significance of this innervation is unclear. Following experimentally induced subarachnoid haemorrhage (SAH) in animal models, immunocytochemical studies have revealed that changes occur in the staining intensity of some of these neuropeptides. This study compared the immunostaining intensity of calcitonin-gene-related peptide (CGRP) and substance P (SP) in cerebral and dural perivascular nerve fibers after SAH in the rat. Subarachnoid haemorrhage was produced by injecting 0.3 ml of autologous blood into the cisterna magna of male Sprague Dawley rats. Sham operated animals received an equal volume of buffered lactated Ringer's solution (pH 7.4). Changes in the immunostaining intensity of cerebral and dural vessels were evaluated by independent observers at 6, 24, and 48 hours after SAH. Immunostaining of CGRP was reduced in cerebral vessels at 6 hours and returned to normal by 48 hours. In contrast, CGRP immunostaining of dural perivascular nerve fibers was unchanged at all time periods examined. A marked decrease in SP immunostaining was documented at 6 hours in both the cerebral and dural vessels in all animals; at 48 hours, the staining intensity had returned to control levels. These results support the idea that several subpopulations of trigeminovascular neurons containing CGRP, SP, or both project to cerebral and dural vessels. Since these subpopulations may be differentially activated in pathologic conditions, such as SAH or vascular headache, the potential exists for pharmacologic intervention of specific neuropeptides with the resultant abatement of a pathologic process.
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PMID:Effect of subarachnoid haemorrhage on trigeminovascular calcitonin-gene-related peptide and substance P of the rat dura mater versus cerebral vasculature. 752 75

Cerebral vasospasm following subarachnoid hemorrhage was induced in the squirrel monkey in order to evaluate the involvement of cerebrovascular sensory nerves in the development of the vasospasm. A unilateral surgical section of the trigeminal nerve at post- but not at pre-Gasserian level caused constriction of the major ipsilateral cerebral arteries. A pre- or postganglionic trigeminal lesion induced an increased glucose uptake globally without influencing the cerebral blood flow. Following a subarachnoid hemorrhage, the decrease in cerebral blood flow was similar of that seen in control animals, while post-ganglionically lesioned animals had an additional increase in glucose uptake. Intrathecal injection of gamma-globulin against substance P prevented the occurrence of vasospasm and the decrease in cerebral blood flow, while calcitonin gene-related peptide (CGRP) anti-gamma-globulin injection significantly reduced the resting vessel diameter and did not influence spasm development. It is concluded that a nervous reflex mechanism could underlie cerebral vasospasm. The cerebrovascular sensory nerves have both a peripheral and a central function. A peripheral or axon reflex mechanism exerts a tonic effect on the cerebral arteries. Central neurotransmission seems to be involved in the regulation of cerebral metabolism and possibly in the coordination of cerebral blood flow and glucose metabolism. CGRP could be the transmitter involved in a peripheral axon reflex and substance P might be the neurotransmitter conveying information to the brainstem vascular centers.
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PMID:Cerebrovascular sensory innervation involved in the development of cerebral vasospasm following a subarachnoid hemorrhage. 753 Jul 34

INTRODUCTION--Cerebral blood vessels are innervated by sympathetic nerve fibres storing neuropeptide Y (NPY), parasympathetic nerves storing acetylcholine, vasoactive intestinal peptide (VIP) and sensory afferent fibres containing calcitonin gene-related peptide (CGRP), substance P (SP) and neurokinin A. In experimental studies on subarachnoid haemorrhage (SAH) there are indications that perivascular peptides are involved. In the present study we have in man measured the levels of NPY, VIP, SP and CGRP in brain vessels of patients that have suffered a fatal SAH and compared this with the levels encountered in subjects that died of an extracerebral cause. MATERIAL AND METHODS--Vessels from patients who have died from SAH or nonSAH were obtained during autopsy performed within 24 hrs after death. The peptides were extracted and fractionated with reversed phase liquid chromatography (HPLC). The levels of NPY, VIP, SP, and CGRP were measured with radioimmunoassay. Vasomotor responses of human cerebral arteries were performed using a sensitive in vitro system. RESULTS--Human cerebral vessels contained NPY, VIP, CGRP and SP which eluted at the same positions as the authentic peptides. The level of CGRP was significantly lower (p < 0.01) in arteries removed from SAH patients as compared to control subjects. The level of SP was not changed, if anything it tended to be increased after SAH. The levels of NPY and VIP were not significantly altered after SAH. In isolated brain vessels alpha-CGRP was a potent vasodilator of arteries precontracted with whole blood, prostaglandin F2 alpha or endothelin. It had a poor effect on vessels precontracted with 60 mM potassium. CONCLUSION--The evidence suggest that the trigemino-cerebrovascular system, storing CGRP and SP, is to a differential degree involved in the pathophysiology of SAH in man and supports the hypothesis of an exhaustion of CGRP as one important factor in the development of late spasm occurring after SAH.
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PMID:Perivascular neuropeptides (NPY, VIP, CGRP and SP) in human brain vessels after subarachnoid haemorrhage. 753 26

A possible involvement of perivascular vasodilatory neuropeptides in subarachnoid haemorrhage (SAH) has been evaluated in man by measuring the levels of calcitonin gene related peptide (CGRP)-, substance P (SP)- and vasoactive intestinal peptide (VIP)-like immunoreactivity (LI) in the cranial venous outflow and in CSF in 34 patients admitted to the hospital after an acute SAH. After operation with aneurysm clipping and nimodipine treatment, blood samples were taken from the external jugular vein (EJV) or cerebrospinal fluid (CSF) and analysed for neuropeptide levels with specific radioimmuno assays (RIA) during the postoperative course. The degree of vasoconstriction in the patients was monitored with Doppler ultrasound recordings bilaterally from the middle cerebral (MCA) and internal carotid arteries (ICA) following the EJV blood sampling every second day. The mean value of all CGRP-LI measurements in EJV during the entire course of SAH (n = 20) revealed a significantly higher level as compared to controls. The highest CGRP-LI levels were found in patients with the highest velocity index values (vasospasm). The relationship Vmean MCA/Vmean ICA was used as an index of vasoconstriction. In patients with MCA aneurysms (n = 10), a significant correlation (r = 0.65, p < 0.05) was found between the vasospasm index and CGRP-LI levels. There were no changes observed in the SP- and VIP-LI levels. Alterations in cerebrovascular tone induced by changing arterial CO2 tension or lowering of blood pressure (ketanserin infusion test) did not alter the levels of the perivascular peptides in the EJV. In addition, CGRP-, SP-, VIP- and neuropeptide Y (NPY)-LI were analysed in CSF in the post-operative course after subarachnoid haemorrhage (SAH) in 14 patients. The CSF VIP-LI was lower in SAH than in control (p < 0.05). The CGRP-LI level was measurable in SAH CSF but not in CSF of controls. In individual patients with marked vasoconstriction increased levels of CGRP-LI (up to 14 pmol/L) and NPY-LI (up to 232 pmol/L) were observed. The results of this study are in support of our hypothesis that there is an involvement of the sensory peptide CGRP in a dynamic reflex aimed at counterbalancing vasoconstriction in SAH.
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PMID:Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid haemorrhage in man. 753 26

To investigate the effects of subarachnoid hemorrhage (SAH) on the responsiveness of human cerebral arteries to vasoactive substances, the authors measured the isometric tension generated in helical strips of basilar and middle cerebral arteries isolated from human cadavers. Contractions caused by KCl, prostaglandin F2 alpha, noradrenaline, and serotonin were reduced in arteries obtained from cadavers with aneurysmal SAH damage and compared to those obtained from cadavers with no indication of intracranial diseases. Endothelium-dependent relaxation elicited by substance P and bradykinin, and endothelium-independent relaxation induced by prostaglandin I2 and nitroglycerin were also markedly decreased in arteries affected by SAH. However, the reduction in relaxation response to prostaglandin I2 was significantly less than that to the other vasodilator agents. These results indicate that human cerebral artery functions are severely impaired after SAH and that poor responses to vasoactive agents may result primarily from dysfunction of smooth-muscle cells.
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PMID:Altered reactivity of human cerebral arteries after subarachnoid hemorrhage. 754 26

Experimental SAH in the squirrel monkey induces an angiographically demonstrable late spasm of about 23% at six days post subarachnoid haemorrhage (SAH). The late spasm is associated with a generalized reduction in cerebral blood flow (CBF) of about 30%. Intracisternal administration of the substance P (SP) antagonist spantide two hours and three days post SAH significantly reduces the degree of late spasm and also decreases the degree of CBF reduction. The findings suggest that SP is involved in the development of both angiographical spasm and CBF changes post SAH.
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PMID:Effect of spantide, a substance-P antagonist, on cerebral vasospasm in primates. 768 6


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