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)

We have recently shown that the novel neuropeptide calcitonin gene-related peptide, CGRP, is a potent vasodilator. In this paper we report a detailed study of the effects of CGRP in human skin. CGRP induces a clearly defined, long-lasting erythema. We have measured the effect of CGRP on blood flow in human skin using a laser Doppler technique and have demonstrated increased local blood flow that persists for a number of hours. We compared the response of CGRP with other known vasodilators [histamine, prostaglandin (PG) E2, PGI2, substance P, and vasoactive intestinal peptide (VIP)] in the skin, and in all subjects the erythema induced by CGRP was more persistent than that induced by the other mediators tested. Except at high doses the local vasodilatation induced by CGRP was not associated with a wheal and flare as seen with histamine, substance P, and VIP. CGRP is an extremely potent vasodilator and if released into the circulation, or locally from peripheral nerve endings, it could have a role in the regulation of blood flow in both physiologic and pathologic conditions; CGRP may be the endogenous mediator of the flare in the triple response. A deficiency in CGRP secretion or action could be an important component of peripheral vascular disease. Some flushing reactions (e.g., those associated with medullary thyroid carcinoma) may result from circulating CGRP.
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PMID:Potent vasodilator activity of calcitonin gene-related peptide in human skin. 242 85

Immunocytochemistry for the general neuronal marker protein gene product 9.5 and four neuropeptides (calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide and neuropeptide Y) was performed on 20 skin biopsy specimens from 19 diabetic patients, age range 20-75 years, 17 Type 2 (non-insulin-dependent) and 3 Type 1 (insulin-dependent). Fifteen specimens were from the lower limb, 3 from the upper limb and 2 from the abdominal wall. Seven subjects had lower limb neurophysiological tests. All but one specimen showed reduced protein gene product 9.5 and neuropeptide immunoreactivity. Reduced protein gene product 9.5 and neuropeptide immunoreactivity was found in specimens taken from the abdominal wall and hand as well as those from the leg, and also in specimens from patients undergoing amputation for peripheral vascular disease. In general, the greater the number of abnormal neurophysiological tests, the greater the extent of neuronal abnormalities. Three patients with normal tests had abnormalities of dermal innervation. While these changes are also found in other axonal neuropathies, in the absence of other causes of peripheral nerve disease and of macrovascular disease, immunocytochemistry of skin biopsies may have a role in the assessment of diabetic neuropathy and its response to treatment.
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PMID:Depletion of cutaneous nerves and neuropeptides in diabetes mellitus: an immunocytochemical study. 247 7

Electrical spinal cord stimulation (SCS) is an important method in the treatment of certain chronic pain syndromes which are difficult to manage with conventional techniques. The indications for this procedure have gradually narrowed to neuropathic pain states, especially those of peripheral origin, ischaemic pain due to peripheral vascular disease, and treatment-resistant angina pectoris. In spite of the clinical use of this method for more than 20 years, the mechanisms underlying the pain alleviating effect remain largely unknown. For the effect on ischaemic pain, recent animal research indicates a mediation via autonomic pathways. Concerning the effect on neuropathic pain progress in knowledge has been scanty. Data from spinal microdialysis in decerebrated or anaesthetized animals indicate the possible importance of serotonin and substance P in the dorsal horn for pain inhibition by SCS. However, data from experiments on anaesthetized animals are, for several reasons, not likely to truely reflect the mechanisms active in conscious humans under treatment with SCS. To avoid the influence of anaesthesia and to approach the clinical situation, we have developed an animal model enabling simultaneous SCS and supraspinal microdialysis in awake, freely moving rats. The animal model is described and some preliminary data indicating a release of gamma-amino butyric acid (GABA) induced by SCS in the periaqueductal grey matter (PAG), are presented.
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PMID:An animal model for the study of brain transmittor release in response to spinal cord stimulation in the awake, freely moving rat: preliminary results from the periaqueductal grey matter. 790 75

Dorsal column stimulation (DCS) is used clinically to provide pain relief from peripheral vascular disease and has the benefit of increasing cutaneous blood flow to the affected lower extremities. The purpose of this study was to examine the role of dorsal roots, calcitonin gene-related peptide (CGRP), and substance P in the cutaneous vasodilation induced by DCS. Male rats were anesthetized with pentobarbital sodium (60 mg/kg ip). A unipolar ball electrode was placed unilaterally on the spinal cord at the L1-L2 spinal segment. Blood flow was recorded in each hindpaw foot pad with laser Doppler flowmeters. Blood flow responses were assessed during 1 min of DCS (either 0.2 mA subdural or 0.6 mA epidural at 50 Hz, 0.2-ms pulse duration). Dorsal rhizotomy of L3-L5 (n = 5) abolished the cutaneous vasodilation to subdural DCS, whereas removal of T10-T12 (n = 5) and T13-L2 dorsal roots (n = 5) did not attenuate the DCS-induced vasodilation. The CGRP antagonist, CGRP-(8-37) (2.6 mg/kg iv, n = 7), eliminated the epidural DCS-induced vasodilation, whereas the substance P receptor antagonist, CP-96345 (1 mg/kg iv, n = 6), had no effect. In summary, L3-L5 dorsal roots and CGRP are essential for the DCS-induced vasodilation. We propose that DCS antidromically activates afferent fibers in the dorsal roots, thus causing peripheral release of CGRP, which produces cutaneous vasodilation.
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PMID:Cutaneous vasodilation during dorsal column stimulation is mediated by dorsal roots and CGRP. 912 59