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)

Bradykinin, substance P and vasopressin induced a vasodilatation followed by a vasoconstriction in control perfused canine basilar arteries with endothelium. The dilatation was significantly reduced and the constriction was significantly enhanced by endothelial removal with saponin. The potentiated constriction was significantly blocked by sodium ozagrel, a thromboxane synthetase inhibitor. These results suggest that the dilatation due to these neuropeptides may depend on endothelium-derived relaxing factor, and that the augmented constriction after endothelial removal may be related to the thromboxane A2 production in cerebral arterial smooth muscles. This mechanism following the damage of endothelium might be implicated in cerebral vasospasm after subarachnoid haemorrhage.
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PMID:Origin of thromboxane-mediated constriction due to neuropeptides in canine basilar artery. 782 46

The stainless steel cannula method was applied to isolated and perfused canine basilar arteries to examine the role of endothelium in the responses to intraluminal vasoactive substances. After intraluminal treatment with saponin to remove the endothelium, the monophasic constrictions to potassium chloride and prostaglandin F2 alpha were potentiated, while those to phenylephrine (alpha 1-adrenoceptor agonist) and 5-hydroxytryptamine were not changed. Xylazine (alpha 2-adrenoceptor agonist) and acetylcholine induced a constriction preceded by a small dilation in controls. The response to xylazine was not modified, while the constriction to acetylcholine was augmented after endothelium removal. Bradykinin, substance P and vasopressin caused a dilation in lower doses, and a dilation followed by a secondary constriction in higher doses in controls. The dilations to these peptides were reduced and the constrictions were enhanced after endothelial removal. Adenosine triphosphate produced a biphasic response, i.e., a dilation followed by a constriction, which was occasionally preceded by a small constriction in higher doses, and only the dilation in lower doses was attenuated. The monophasic dilation to adenosine was potentiated, while the papaverine-induced dilation was not influenced by endothelial removal. After extraluminal treatment with oxyhemoglobin, the dilations to calcium ionophore A23187 and thimerosal were attenuated, while the constriction to acetylcholine was enhanced. The dilations to substance P and vasopressin were depressed, and the constrictions were potentiated. The monophasic dilation to sodium nitroprusside was augmented, while that to papaverine was not changed. These results suggest that the endothelium may play important roles not only in producing endothelium-derived relaxing factors but also in modulating the calcium influx into the smooth muscle cells. The mechanisms of altered responsiveness might be implicated in cerebral vasospasm following subarachnoid hemorrhage.
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PMID:Effects of endothelium removal by saponin and of oxyhemoglobin on canine cerebrovascular responses. 783 71

Calcitonin gene-related peptide (CGRP) is a neuropeptide co-stored with tachykinins (substance P, neurokinin A) in cerebrovascular sensory fibers in the trigeminal ganglion. Preceding studies on subarachnoid hemorrhage (SAH) revealed that an enhanced release of CGRP resulted in the selective loss of perivascular CGRP. Therefore, the present study was designed to evaluate the effects of intravenous administration of human alpha-CGRP on cerebral vasoconstriction in the postoperative course after SAH in 5 patients (8 infusions). Cerebral vasoconstriction was evaluated with transcranial Doppler sonography. The increase in the relationship between middle cerebral artery (MCA) velocity and internal carotid artery (ICA) velocity (the hemodynamic index) was used as an indicator of vasoconstriction and compared to the contralateral side. A significant reduction was found in the hemodynamic index during the CGRP infusion (4.3 +/- 0.5, P < 0.05) as to compared to before infusion (6.2 +/- 0.5). There was no measurable change in the hemodynamic index on the contralateral side. No significant change was observed in pulsatility index, blood pressure or consciousness during the peptide infusion. A significant increase in heart rate was observed during the infusion as compared to before and after infusion (90 +/- 4 vs. 76 +/- 5). Cardiac ultrasound data indicated a mean cardiac output increase of 1.9 liter/min, and a mean decrease in total peripheral resistance of 538 dynes s/cm5. The results obtained show that infusion of human alpha-CGRP may induce normalisation of cerebrovascular tone in SAH.
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PMID:Calcitonin gene-related peptide (human alpha-CGRP) counteracts vasoconstriction in human subarachnoid haemorrhage. 804 16

The effect of subarachnoid hemorrhage (SAH) on the neuropeptides and mast cells of the rat dura mater has not been reported. We examined the outcome of SAH on the rat supratentorial dura mater to determine whether dural nerves undergo effects similar to those of nerves accompanying cerebral blood vessels after SAH. Following the injection of fresh autologous arterial blood into the cisterna magna, animals were sacrificed at 6, 24, and 48 h, and 6 days post-SAH. Dural whole mounts were immunohistochemically reacted with antibodies to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and serotonin (5-HT). SP-like immunostaining was substantially reduced after SAH and subsequently returned to control levels at 6 days. NPY-like fiber innervation of the dura was markedly reduced after SAH; although immunostaining intensity increased, it had not returned to control levels at 6 days. The 5-HT content of dural mast cells identified by immunostaining markedly decreased at 6 and 24 h and returned to control levels at 48 h. In contrast, CGRP immunostaining was unchanged in all experimental groups. One possible explanation for this differential response is that subpopulations of trigeminovascular neurons containing SP, CGRP, or CGRP and SP respond differently to various stimuli, including SAH. Another possibility is a differential release of SP or CGRP from the same fiber. To the best of our knowledge this is the first documentation that the dura is also a target for intracranial pathological processes, such as SAH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dural neuropeptide changes after subarachnoid hemorrhage in rats. 851 60

Cisternal injections of blood in the rat and squirrel monkey produce an angiographically demonstrable biphasic vasospasm with a maximal late spasm at two days in the rat and six days post-subarachnoid hemorrhage (SAH) in the monkey. The SAH induces a decrease in cerebral blood flow of about 25% and a corresponding increase in glucose uptake of between 30% and 50%. In about half of the animals low-flow areas were noted in the cortex and the basal ganglia with a corresponding marked increase in glucose uptake. Lesioning of the A2-nucleus, its ascending pathway or the median eminence prevents the occurrence of spasm. Similarly, treatment with a substance P antagonist or gammaglobulin against substance P prevents or significantly reduces the degree of spasm. A unilateral post-ganglionic trigeminal lesion causes an ipsilateral constriction of the cerebral arteries of 27%, while a preganglionic lesion does not affect the baseline diameter. A pre- or post-ganglionic trigeminal lesion induces an increase in glucose uptake globally of about 50% without influencing cerebral blood flow. Following SAH the decrease in blood flow in both groups of lesioned animals is similar to that seen in controls. After SAH there is no further change in glucose uptake in the animals with a preganglionic lesion, while in the post-ganglionically lesioned animals there is an additional increase in glucose uptake of about 50% as compared to controls or the animals with a preganglionic lesion.
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PMID:Trigeminal afferents and brainstem centers involved in the occurrence of cerebral vasospasm. 891 53

Cisternal blood injection in the rat and squirrel monkey produces a biphasic cerebral vasospasm, a decrease in cerebral blood flow (CBF) and an increase in glucose uptake (CMRglu) due to an anaerobic glucolysis actually representing a decrease in metabolism. Lesioning of the A2-nucleus, its ascending cathecolamine pathways or their projection site, the median eminence in the hypothalamus, prevents the occurrence of spasm. A unilateral postganglionic trigeminal lesion causes an ipsilateral constriction of the cerebral arteries while a preganglionic lesion does not affect the baseline arterial diameter. Both kinds of trigeminal lesions induce a global increase in glucose uptake of about 50% without influencing CBF. Following subarachnoid hemorrhage (SAH) the decrease in CBF in both groups of lesioned animals is similar to that seen in controls. After SAH there is no further change in CMRglu in the animals with a preganglionic lesion, while in the postganglionically lesioned animals there is an additional increase in CMRglu of about 50% as compared to controls or animals with a preganglionic lesion. Treatment with the peptidergic substance P (SP) antagonist, spantide, or gammaglobulin against SP prevents or significantly reduces the degree of spasm and the changes in flow and metabolism normally seen post-SAH. The non-peptidergic neurokinins NK1 and NK3 antagonists do not influence flow and metabolism in SAH animals. The NK2 seems to change both flow and metabolism post-SAH in rats.
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PMID:Trigeminal nerve and brainstem catecholamine systems in cerebral vasospasm. 1023 97

Peptidergic innervation of the human cerebral vasculature has not yet been described in detail and its role in the maintenance of cerebral autoregulation still needs to be established. Similarly, few data exist on the innervation of vascular malformations. The aim of this study was to clarify the peptidergic innervation patterns of human cerebral arteries of various sizes, and, for the first time, that of saccular aneurysms. Light microscopic study of whole-mount preparations of human cerebral arteries and aneurysm sacs resected either during tumor removal or after neck-clipping were carried out by means of silver-intensified light microscopic immunocytochemistry visualizing neuropeptide-Y, calcitonin gene-related peptide and substance P immunoreactivity. Systematic morphological investigations confirmed the presence of longitudinal fiber bundles on the adventitia and a network-like deeper peptidergic system at the adventitia-media border, while in smaller pial and intraparenchymal vessels, only sparse longitudinal immunopositive axons could be detected. The innervation pattern was totally absent in the wall of saccular aneurysms with the complete disappearance of peptidergic nerve fibers in some areas. To the best of our knowledge neither the disappearance of this network on small pial and intraparenchymal vessels, nor the absence of an innervation pattern in saccular aneurysms have been described before. Nonhomogeneous peptidergic innervation of the human cerebral vascular tree might be one of the factors responsible for the distinct autoregulatory properties of the capacitance and resistance vessels. Malfunction of this vasoregulatory system might lead to the impairment of autoregulation during pathological conditions such as subarachnoid hemorrhage.
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PMID:Peptidergic innervation of human cerebral blood vessels and saccular aneurysms. 1050 44


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