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

Calcitonin gene-related peptide (CGRP) is cleaved by an endopeptidase, also known to hydrolyze substance P (SP). The enzyme which was isolated from human cerebrospinal fluid, converted rCGRP into two products, clearly separable on HPLC. Amino acid analysis showed cleavage to occur at Leu16-Ser17. The carboxy-terminal fragment, rCGRP-(17-37), was weakly active in inhibiting 125I-rCGRP binding to a rat medulla oblongata membrane preparation, but it showed no binding to spinal cord membranes. The N-terminal fragment, rCGRP-(1-16), had very low or no affinity. Autoradiography with 125I-rCGRP showed distinct labelling of rat dorsal spinal cord, while there was no consistent pattern with 125I-rCGRP-(1-16). In the isolated guinea pig ileum preparation, the two fragments showed no CGRP-like activity. The ability of CGRP to interfere with SP degradation is offered as the explanation why CGRP has been reported to potentiate several biologic actions of SP.
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PMID:Calcitonin gene-related peptide is metabolized by an endopeptidase hydrolyzing substance P. 247 92

Vascular leakage in the middle ear cavity was studied after i.v. administration of various substances in rats and determined by the Evans blue technique. Bradykinin, histamine, serotonin, acetylcholine, substance P (SP) and vasoactive intestinal polypeptide (VIP) resulted in extravasation of Evans blue. In the case of bradykinin and histamine, the leakage was dose dependent. Calcitonin gene-related peptide (CGRP) did not affect vessel permeability. In other experiments the effect of histamine antagonists was tested on production of middle ear effusion, caused by blowing air at 14 degrees C into the external auditory canal (EAC). The increase in vessel permeability in this otitis media model was inhibited by the H2-receptor antagonist cimetidine, at doses 0.1 and 1.0 mg/ml. Diphenhydramine, an H1-receptor antagonist, arrested only partly middle ear fluid accumulation. Our study demonstrated that various inflammatory mediators and neuropeptides are capable of inducing vascular leakage in the middle ear cavity. It was also concluded that H2-receptors are involved in the regulation of middle ear vascular permeability.
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PMID:Middle ear effusion induced by various inflammatory mediators and neuropeptides. An experimental study in the rat. 247 18

1. The effects of capsaicin, calcitonin gene-related peptide and substance P were studied via three parameters in the guinea-pig vas deferens: the overflow of ATP and of tritiated noradrenaline, the mechanical responses to field stimulation and the mechanical responses to exogenous noradrenaline and alpha, beta-methylene ATP. 2. At 2 Hz, capsaicin inhibited the stimulus-evoked release of ATP, whereas it was without effect on the release of noradrenaline. At 20 Hz capsaicin did not affect the release of either of the cotransmitters. Capsaicin enhanced responses to alpha, beta-methylene ATP, but not to exogenous noradrenaline. 3. Calcitonin gene-related peptide, like capsaicin, inhibited the release of ATP, but not noradrenaline at 2 Hz and was without effect on release at 20 Hz. However, calcitonin gene related peptide inhibited responses to alpha, beta-methylene ATP and was without effect on responses to exogenous noradrenaline. 4. Substance P had no effect on the release of either noradrenaline or ATP at either frequency. However, like capsaicin it enhanced responses to alpha, beta-methylene ATP and was without effect on exogenous noradrenaline. 5. These results suggest that the actions of capsaicin on the guinea-pig isolated vas deferens are mediated via the release of both calcitonin gene-related peptide and substance P. Furthermore, as capsaicin and calcitonin gene-related peptide prejunctionally modulate purinergic, but not noradrenergic transmission, this suggests that the mechanisms for the storage and release of the sympathetic co-transmitters noradrenaline and ATP may not be the same.
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PMID:Modulation of neurotransmission in the guinea-pig vas deferens by capsaicin: involvement of calcitonin gene-related peptide and substance P. 247 44

Calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity were investigated in the superior cervical ganglion of normotensive and genetically hypertensive Otago Wistar rats by an immunoperoxidase method. CGRP- and SP-positive varicose axons invested separate subpopulations of ganglion cells, neither of which contained neuropeptide Y. The densities of CGRP axons were similar in normotensive and hypertensive rats while the numbers of SP axons were several times higher in the hypertensive strain. Decentralization of the ganglion or chronic capsaicin treatment removed all immunoreactive terminals, indicating that both axon populations are likely to be collaterals from thoracic sensory afferents.
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PMID:Different patterns of immunolocalization of calcitonin gene-related peptide and substance P in sympathetic ganglia of normotensive and genetically hypertensive rats. 247 93

The noradrenergic and peptidergic innervation of the extrinsic vessels and microcirculation of the rat cremaster muscle was examined. Catecholamine-containing nerves were identified histochemically by glyoxylic acid-induced fluorescence and tyrosine hydroxylase immunoreactivity (TH-IR). The extrinsic pudic-epigastric artery and vein as well as the entire intramuscular arteriolar network was innervated by noradrenergic axons. The capillaries and intramuscular venules of the cremaster muscle were devoid of a noradrenergic innervation. Immunohistochemical double-labeling demonstrated that most, if not all, of the TH-IR axons also possessed neuropeptide Y immunoreactivity (NPY-IR), implying colocalization of the norepinephrine and NPY in the perivascular nerves. No vasoactive intestinal peptide immunoreactivity (VIP-IR) was found, except for occasional VIP-IR axons associated with the pudic-epigastric artery. Substance P immunoreactive (SP-IR) axons formed a sparse plexus around the arteries and larger arterioles. Calcitonin gene-related peptide immunoreactivity (CGRP-IR) had a similar distribution to the SP-IR axons. CGRP-IR was also observed in axons alongside some smaller arterioles and capillaries. The extrinsic vessels and intramuscular arteriolar network of the rat cremaster muscle are innervated by noradrenergic axons which contain NPY and by presumed sensory nerves containing SP and/or CGRP. Both types of nerves may contribute to regulation of microvascular function.
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PMID:Noradrenergic and peptidergic innervation of the extrinsic vessels and microcirculation of the rat cremaster muscle. 248 4

Putative neurotransmitters of the lower urinary tract were investigated in apes, rabbits and cats using immunohistochemical techniques of PAP (Peroxidase antiperoxidase) staining and IGSS (Immunogold silver staining) methods for Neuron specific enolase (NSE), Acetylcholine (Ach), Noradrenaline (NA), Vasoactive intestinal polypeptide (VIP), Substance P (SP) and Calcitonin gene related peptide (CGRP). 1) The localization of pelvic ganglions exhibited more striking evidence of species difference. Huge pelvic ganglions were found particularly in the dorsolateral area of the prostate in apes. On the other hand, in cats and rabbits, many ganglion cells were found around the uretero-vesical junctions. 2) In the pelvic ganglions of the apes, Ach immunoreactives were detected in nearly 70 percent of the cell bodies. 10-15 percent were NA immunoreactive cells. In addition, 15-20 percent VIP and a smaller percentage of SP immunoreactive cells were detected in the same ganglions. Axons extending from the ganglion cells showed the intense neurotransmitters immunoreactivity. 3) In the apes, varicose fibers containing SP were widely distributed in the epithelium, submucosa, muscle layer, and around the vessels of the bladder. SP immunoreactive cell bodies were found in the dorsal root ganglion at levels of L7, S1 and at the same levels in the posterior horn. On the other hand, the bulbourethral gland and the seminal vesicle contained SP immunoreactive cell bodies. 4) CGRP containing fibers were distributed in similar locations as SP containing fibers in the bladder. 5) VIP immunoreactive fibers were also widely distributed, being most dense at the base of the bladder.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunohistochemical studies of putative neurotransmitters in the lower urinary tract]. 257 46

The presence and distribution of peptide-containing nerve fibres and axon terminals have been studied in the proximal part of the superior mesenteric artery (SMA) (i.e. conductance vessel) and in the finer ramifications of the SMA close to the intestine (outer diameter 200 microns, i.e. resistance vessel). Light microscopic immunocytochemistry revealed that the proximal part of the SMA possessed a rich supply of neuropeptide Y (NPY)- and tyrosine hydroxylase (TH)-immunoreactive nerve fibres, forming a loose perivascular network which increased in density distally. The vasoactive intestinal peptide (VIP) immunoreactivity was moderate in the proximal artery and only a few VIP fibres could be identified in the distal portion of the SMA. Calcitonin gene-related peptide (CGRP)-, neurokinin (NK)- and substance P (SP)-immunoreactive fibres had an intermediate density in both arterial regions, but their distribution pattern varied. Electron microscopic immunocytochemistry showed that NPY-immunoreactive nerve terminals were close to the smooth muscle cells of the medial layer in both parts of the SMA, indicative of a vasomotor role. Although the VIP-immunoreactive terminals had a similar localization they were seen less frequently. CGRP-, NK- and SP-immunoreactive axons had an identical distribution in the two vascular regions. Interestingly, they were usually seen more distant from the medial layer, localized in the adventitia. Examination of vasomotor responses to perivascular peptides revealed significant regional differences: NPY produced only weak contractions (13 +/- 3%) of proximal vessel segment of the conductance type, while strong concentration-dependent contractions were seen in distal parts of the SMA (resistance vessel). In neither region was any interaction with noradrenaline demonstrated. Proximal segments of the SMA revealed a stronger and more potent response to VIP and peptide histidine isoleucine than did distal segments, while on the other hand acetylcholine was more potent and elicited stronger effects in distal segments. CGRP, NKA and SP relaxed precontracted arteries by 50-75% and there was no significant difference in responsiveness to these peptides in the two regions of the SMA.
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PMID:Comparison of peptidergic mechanisms in different parts of the guinea pig superior mesenteric artery: immunocytochemistry at the light and ultrastructural levels and responses in vitro of large and small arteries. 262 2

Calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal polypeptide (VIP) have been proposed to be neurotransmitters/neuromodulators in cerebral perivascular nerve fibers. Here, we present pharmacological and biochemical evidence showing that these peptides have different modes of relaxing cerebral blood vessels in the cat. CGRP causes pronounced relaxation, this occurs simultaneously with stimulation of cyclic adenosine monophosphate (cAMP) accumulation. The strong VIP-induced dilatation is parallelled by cAMP accumulation, albeit of a lower magnitude than with CGRP. The SP-induced relaxation was much weaker than that of CGRP and VIP, and it was not associated with cAMP accumulation. Only at concentrations of SP where maximum relaxation had occurred, was a nonsignificant cAMP accumulation seen. The responses to SP and acetylcholine were absent in arteries where the endothelium had been removed, whereas the relaxations induced by CGRP and VIP persisted.
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PMID:Perivascular peptides relax cerebral arteries concomitant with stimulation of cyclic adenosine monophosphate accumulation or release of an endothelium-derived relaxing factor in the cat. 299 76

Recent evidence suggests that several bioactive polypeptides, among them substance P, neurokinin A, and calcitonin gene-related peptide, are contained in tracheobronchial C-fibers. These peptides can be released from the lung by irritant chemicals or local inflammatory mediators like histamine or bradykinin. Substance P mimics the increase in vascular permeability caused by vagal nerve stimulation and neurokinin A mimics noncholinergic bronchoconstriction by vagal nerve stimulation. Calcitonin gene-related peptide displays vasodilator activity. Experiments carried out with sensitized guinea pigs showed a contribution of tracheobronchial C-fibers to the anaphylactic response. Additionally, capsaicin, which in high concentration selectively blocks sensory C-fibers, was found to be effective in treatment of hyperreactive rhinopathy (vasomotor rhinitis). It is concluded that peptide mediators released from tracheobronchial C-fibers may contribute to the pathophysiology of various allergic or inflammatory airway diseases.
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PMID:Neuroimmune interactions in the airways: implications for asthma, allergy, and other inflammatory airway diseases. 307 81

Calcitonin gene-related peptide (CGRP) in the thyroid has a dual localization to nerve fibers around blood vessels and follicles and to parafollicular (C) cells. CGRP was found to coexist with substance P (SP) in most of the nerve fibers; a few CGRP fibers seemed to lack SP, and a few SP fibers seemed to be devoid of CGRP. In the C cells, CGRP coexisted with calcitonin (CT). Cervical vagotomy (extirpation of the nodose ganglion) eliminated approximately 50% of the CGRP/SP fibers in the thyroid without any overt influence on CGRP/CT in the C cells. Removal of the superior cervical ganglion or chemical sympathectomy (6-hydroxydopamine treatment) affected neither thyroid CGRP/SP nerve fibers nor CGRP/CT-storing C cells. CGRP nerve cell bodies were numerous in the jugular-nodose ganglionic complex (notably in the jugular portion); in many of them, CGRP coexisted with SP. A few scattered CGRP nerve cell bodies also occurred in the laryngeal ganglion, whereas none was found in the thyroid ganglion. Hypercalcemia evoked by vitamin D2 treatment, which is known to degranulate thyroid C cells, reduced the thyroid content of both CGRP and CT. As tested in mice in vivo, CGRP and SP alone or together had no effect on basal or TSH- or isoprenaline-induced thyroid hormone secretion. Vasoactive intestinal peptide-stimulated iodothyronine release, on the other hand, was enhanced by CGRP, but not by SP. SP had no effect on combined vasoactive intestinal peptide-CGRP-stimulated iodothyronine release. These findings suggest that CGRP participates in the control of thyroid hormone secretion and that, like CT, CGRP in the C cells is under control of the serum calcium level.
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PMID:Calcitonin gene-related peptide in thyroid nerve fibers and C cells: effects on thyroid hormone secretion and response to hypercalcemia. 309 6


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