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 innervation of the major arteries and heart of the toad (Bufo marinus) was examined by use of glyoxylic acid-induced catecholamine fluorescence and peptide immunohistochemistry. All arteries possessed a moderate to dense plexus of adrenergic axons, which also showed neuropeptide Y-like immunoreactivity (NPY-LI). Some adrenergic axons in the intracardiac vagal trunks showed NPY-LI, but the varicose adrenergic axons innervating the cardiac muscle of the atria and ventricle, and the coronary blood vessels did not display NPY-LI. About half of the nerve cell bodies in the anterior sympathetic chain ganglia with dopamine-beta-hydroxylase-LI (DBH-LI) also contained NPY-LI. The nerve cell bodies with DBH-LI alone were generally larger (median diameter 30 micron) than those with both DBH-LI and NPY-LI (median diameter 20 micron). Some cell bodies showing DBH-LI alone were surrounded by boutons with NPY-LI but not DBH-LI. Axons that displayed simultaneously both substance P-LI (SP-LI) and calcitonin gene-related peptide-LI (CGRP-LI) also formed a plexus around all arteries studied, being particularly dense around the mesenteric and pulmonary arteries. These axons are most likely sensory since SP-LI was reduced by capsaicin treatment, and nerve cell bodies with both SP-LI and CGRP-LI were found in dorsal root ganglia and the vagal ganglion. A dense plexus of axons showing somatostatin-LI was located around the pulmonary artery and its main intrapulmonary branches. A few nerves with vasoactive intestinal polypeptide-LI were found around the dorsal aorta and pulmonary artery. No perivascular nerves with enkephalin-LI were observed. Reversed-phase, high-pressure liquid chromatography of acid extracts of the large arteries showed that the major peaks of NPY-LI and SP-LI co-eluted with porcine NPY (1-36) and synthetic SP (1-11), respectively. Thus, the location and structure of these peptides in perivascular nerves has been highly conserved during vertebrate evolution.
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PMID:Innervation of the large arteries and heart of the toad (Bufo marinus) by adrenergic and peptide-containing neurons. 241 19

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

Antidromic stimulation of sensory nerves or administration of capsaicin and SP in the guinea-pig induced vascular protein leakage with a similar pattern of distribution in different peripheral organs, characterized by a wide-spread but highly selective occurrence. The protein-extravasation responses in the tissues, following nerve stimulation or i.v. capsaicin, were highly correlated with the concentration of SP-LI. Systemic capsaicin treatment caused an almost total loss of SP-LI in visceral organs, in which the extravasation responses to capsaicin or nerve stimulation were also abolished. The ureter of the guinea-pig was most densely innervated by capsaicin-sensitive sensory nerves, which arrive at the rostral part of the ureter via the inferior mesenteric ganglion. The caudal ureter was mainly innervated from the pelvic nerves. The vascular permeability increase induced by SP or capsaicin was more pronounced in the ureter than in any other organ investigated. SP-LI, TK-LI and CGRP-LI coexist in sensory neurons of the guinea-pig and man, as shown by immunohistochemistry. These three kinds of immunoreactivity were found in sensory cell bodies with similar regional and terminal distribution patterns in both the central and peripheral areas. Systemic capsaicin treatment induced marked reduction of SP- and TK-LI in peripheral organs except for the ileum. CGRP-LI in the ureter was also sensitive to the capsaicin treatment. Characterization of the TK-LI (K12) of the guinea-pig ureter and lung, using ion-exchange chromatography and HPLC, demonstrated that at least three immunoreactive components corresponding to NKA, NPK and ELE were present. The major form of SP-LI eluted in the same position as synthetic SP. The NKA- and ELE-like components were also identified by HPLC in water extracts of human ureter. NKB was not detectable in the sensory neurons of the guinea-pig. Capsaicin caused an acute release of SP-, NKA- and ELE-like components from superfused slices of both the spinal cord and ureter of the guinea-pig in vitro. The release of tachykinins by capsaicin was calcium-dependent but tetrodotoxin-resistant. No detectable release of NKB- or NPK-LI was induced by capsaicin. Tachykinins share a common spectrum of biological activities with regard to hypotension, bronchoconstriction and protein extravasation when given systemically to guinea-pigs. The potency of the hypotensive action of tachykinins was similar. NKA and NPK evoked much stronger bronchoconstrictor effects than SP, while SP was more active than NKA in inducing vascular permeability changes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tachykinins and calcitonin gene-related peptide in relation to peripheral functions of capsaicin-sensitive sensory neurons. 243 Apr 27

In vitro superfusion with capsaicin (5 X 10(-7) M) of slices of the dorsal half of the rat spinal cord produced a significant increase in a release of immunoreactive substance P (iSP). Calcitonin gene-related peptide (CGRP: 10(-6) M) significantly potentiated the capsaicin-induced release of iSP. On the other hand, when CGRP (5 nmol/rat) was intrathecally injected, the peptide produced a significant hyperalgesia to mechanical noxious stimuli (pinching the hind paw), but aversive responses and potentiation of substance P-induced aversive responses were never observed. These findings suggest that in the rat spinal dorsal horn, CGRP potentiates the release of substance P from the primary afferent terminal and promotes the transmission of nociceptive information induced by mechanical noxious stimuli.
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PMID:Calcitonin gene-related peptide promotes mechanical nociception by potentiating release of substance P from the spinal dorsal horn in rats. 243 72

Using a double labeling indirect immunofluorescent technique, we studied the guinea pig trigeminal ganglion and eye for co-localization of substance P and calcitonin gene-related peptide. In the trigeminal ganglion, the number of neurons immunoreactive for calcitonin gene-related peptide significantly outnumber those immunoreactive for substance P, but virtually all substance P positive neurons are immunoreactive for calcitonin gene-related peptide. In the eye, a complex pattern of co-localization is present; both peptides co-localize in most immunoreactive nerve fibers. Nerve fibers immunoreactive only for calcitonin gene-related peptide tend to be concentrated in the cornea and posterior ciliary body. Nerve fibers immunoreactive only for substance P are present in relation to both iris muscles. Sensory denervation by intracranial transection of the ophthalmic and maxillary nerves fails to eliminate these substance P positive but CGRP negative iris nerve fibers. These findings indicate an alternative origin for substance P immunoreactive nerves supplying the iris muscles in this species.
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PMID:Distinct substance P and calcitonin gene-related peptide immunoreactive nerves in the guinea pig eye. 244 7

The vasodilator effects of the human calcitonin gene-related peptides alpha (hCGRP alpha) and beta (hCGRP beta) were studied in vitro and in vivo in relation to the effects of substance P (SP) and capsaicin on coronary vascular tone in the pig. Both hCGRP alpha and -beta induced a concentration-dependent, long-lasting relaxation of precontracted small (diameter 0.5 mm) pig coronary arteries in vitro. SP was slightly more potent but caused a transient relaxation with a smaller maximal response than CGRP. The relaxation induced by hCGRP alpha and -beta as well as SP was resistant to propranolol and atropine. Capsaicin also induced a long-lasting relaxation of potassium and PGF2 alpha-precontracted coronary arteries. After tachyphylaxis to SP had developed the relaxant effects of CGRP and capsaicin were unchanged. Rubbing the vessels to remove the endothelium completely abolished the relaxant effects of SP while the vasodilation induced by hCGRP alpha as well as capsaicin remained unchanged. Injections of hCGRP alpha, SP or capsaicin into the constantly perfused left anterior descending coronary artery of the pig in vivo caused a dose-dependent decrease in perfusion pressure, suggesting coronary vasodilation. In conclusion, the vasodilator effects of SP in vitro differ from the response to CGRP both with regard to their transient nature, the development of tachyphylaxis and endothelium dependence. The capsaicin-induced coronary vasodilation is therefore more likely to depend on release of CGRP rather than tachykinins from sensory nerves since neither endothelium removal nor SP-tachyphylaxis influenced the capsaicin and CGRP responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcitonin gene-related peptide but not substance P mimics capsaicin-induced coronary vasodilation in the pig. 244 87

The present study examines the effects of intrathecal administration of selected peptides on nociceptive responses in the rat. Each peptide was delivered via a chronically implanted catheter to the L5 vertebral level. In the tail flick test, VIP (0.65-6.5 nmoles) produced a dose-dependent decrease in reaction time (RT) from 1 to 6-16 min after injection; 6.5 nmoles decreased RT to 37% of control value at 1 min after injection. Galanin (0.65-6.5 nmoles) produced a dose-dependent increase in reaction time at 1 and 6 min; at high doses, many of the rats failed to flick the tail. CGRP (6.5 nmoles) produced a small, transient decrease in RT to 73% of control values at 1 min; 3.25 nmoles were without effect. CSF and 6.5 nmoles of somatostatin, TRH and angiotensin II were without effect. At high doses of galanin and CGRP, rats vocalized to innocuous touch of the tail, as reported for substance P. Von Frey hairs were thus applied to the tail after 6.5 nmoles of VIP, galanin, CGRP or substance P. Vocalization in response to a previously innocuous pressure stimulus was observed at 30 s after injection in all rats given galanin and some rats given CGRP or substance P; the effect lasted 4-8 min. VIP and CSF had no effect. These results suggest that VIP, galanin, CGRP and substance P may act as excitatory agents in nociceptive pathways and that specific peptides may function in the different types of pain modalities; VIP in thermal, galanin in mechanical and substance P and CGRP in both.
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PMID:Effects of intrathecal administration of neuropeptides on a spinal nociceptive reflex in the rat: VIP, galanin, CGRP, TRH, somatostatin and angiotensin II. 245 92

Capsaicin (1 microM) produced, after an initial contraction, a depression of the field stimulation-induced contraction of the guinea-pig isolated ileal longitudinal muscle. Both effects exhibited prompt desensitization, indicating the involvement of a specific action on sensory nerves. The initial contraction was inhibited by [D-Pro4,D-Trp7,9,Phe11]SP-(4-11), a substance P (SP) antagonist, which did not affect the inhibitory component of the response. Incubation of the strips with antiCGRP (CGRP = calcitonin gene-related peptide) serum did not modify the amplitude of the capsaicin-induced contraction but inhibited the twitch depression induced by capsaicin. AntiCGRP serum blocked the effects of exogenous CGRP but not the inhibitory response induced by baclofen. These findings provide evidence that the release of several neuropeptides from sensory nerves determines the visceromotor response to capsaicin in this preparation. In particular, a CGRP-like peptide could be responsible for the inhibitory phase which follows the initial contraction which is due to release of SP and/or related peptides.
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PMID:Several neuropeptides determine the visceromotor response to capsaicin in the guinea-pig isolated ileal longitudinal muscle. 245 31

The contractile effects of substance P and human calcitonin gene-related peptide (human CGRP) on isolated human intracervical arteries were studied. Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 14) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Neither compound affected resting tension. Both peptides showed potent relaxing effects on vessels precontracted by noradrenaline 10(-5) M. Substance P exhibited the higher potency, while human CGRP showed the higher efficacy. The relaxing effects of the two compounds were unaffected by pretreatment with indomethacin 10(-6) M, propranolol 10(-6) M and atropine 10(-6) M. The results support a role for the two peptides in the regulation of cervical blood flow.
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PMID:Effects of human calcitonin gene-related peptide and substance P on human intracervical arteries. 245 71

The origin of tachykinin- and calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerve fibres in the guinea pig carotid body and carotid sinus was determined by retrograde labelling of the carotid sinus nerve with Fluoro-gold and immunohistochemical double staining with fluorescein- and rhodamine-conjugated second antisera. Fluoro-gold-labelled perikarya with characteristic features of primary sensory neurones were numerous in the glossopharyngeal (petrosal) ganglion and occurred rarely in the closely attached superior vagal (jugular) ganglion. An efferent pathway from the brainstem could not be detected. Co-existence of tachykinin- and CGRP-LI was observed in 25-47% of labelled sensory neurones; less than 1% of Fluoro-gold-containing perikarya were exclusively stained by CGRP antiserum. Co-existence of tachykinin- and CGRP-LI was also demonstrated in nerve fibres of the carotid body and carotid sinus. Somatostatin-, cholecystokinin- and dynorphin-LI did not co-exist with tachykinin-LI in these fibres. Thus, tachykinin/CGRP-LI fibres in the carotid presso- and chemoreceptive areas exhibit a peptide pattern being generally characteristic for sensory fibres supplying great vessels in the guinea pig. In view of the present findings doubt is raised as to a primary involvement of these fibres in presso- or chemoreception, although a modulatory influence on these specific functions appears to be likely.
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PMID:Retrograde neuronal labelling and double-staining immunohistochemistry of tachykinin- and calcitonin gene-related peptide-immunoreactive pathways in the carotid sinus nerve of the guinea pig. 245 82


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