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)

The actions and interactions of putative mediators of inflammation, such as substance P (SP), histamine, bradykinin and prostaglandins (PGE2) were studied in human skin. In addition, the effects of capsaicin were examined as it is known to release (and to deplete) SP and calcitonin gene-related peptide from C-fibres. The flare evoked by bradykinin was abolished by pretreatment with lignocaine (local anesthetic), compound 48/80 (mast-cell histamine liberator), mepyramine (H1-receptor antagonist) and indomethacin (cyclo-oxygenase inhibitor) but was unaffected by atropine and ketanserin (serotonin antagonist). The weal response was not reduced by any of the drugs. The flare evoked by capsaicin was abolished by lignocaine and indomethacin but was unaffected by compound 48/80, mepyramine, atropine and ketanserin. The weal response was reduced by indomethacin. The flare response to bradykinin seems to reflect the activation of C-fibres and associated mast cells, while the flare response to capsaicin seems to reflect the activation of C-fibres only. Repeated injections of capsaicin and bradykinin produced tachyphylaxis (and cross-tachyphylaxis) and greatly reduced the SP-evoked flare. Capsaicin produced tachyphylaxis also after treatment of the skin with a local anaesthetic, suggesting that it develops independently of C-fibre impulse flow. The tachyphylaxis produced by bradykinin and capsaicin seems to reflect the depletion of messenger peptides from the C-fibres. The flare response to SP following capsaicin- or bradykinin-induced desensitization gradually returned to normal after 5-8 weeks. The erythema evoked by PGE2 was reduced by 30% following pretreatment with lignocaine, mepyramine or compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of capsaicin, bradykinin and prostaglandin E2 in the human skin. 137 95

Substance P is a neuropeptide (contained in/and released from the A delta and C nerve fibers of the skin), which provokes erythema, edema, and pruritus after intradermal injection. Local pretreatment with capsaicin produces decreased substance P-dependent erythema, with edema similar to that observed before pretreatment with capsaicin. We injected histamine and in a parallel experiment, substance P in five volunteers before and after local treatment with capsaicin, with 48/80, after 5 days of hydroxyzine. The injection of SP provoked erythema centered by a wheal. After treatment with 48/80, SP provoked increased erythema and a wheal. After hydroxyzine treatment, the injection of histamine produced no erythema or edema in four of the five subjects, while SP provoked erythema in all five subjects and edema similar to that observed before treatment with hydroxyzine. These data support the hypothesis that substance P provokes erythema and edema both with histamine-dependent and histamine-independent pathways.
 ...
PMID:Substance P provokes cutaneous erythema and edema through a histamine-independent pathway. 137 8

We studied substance P-induced cutaneous and bronchial reactions in children with allergic disorders. Furthermore, inhibitory effects of lidocaine on these responses elicited by substance P were also studied. In the intradermal test, children with moderate or severe bronchial asthma showed significantly stronger reactions than controls. In bronchial challenge with substance P, children with bronchial asthma showed an increasing fall in FEV1 and V50 in proportion to the severity of their asthma. Concomitant use of lidocaine significantly inhibited not only substance P-induced intradermal erythema and wheal reactions but air flow limitations. It also inhibited histamine-induced erythema and house dust-induced wheal and erythema reactions. No adverse reactions to lidocaine were observed. These results suggest that substance P might play an important role in cutaneous and bronchial hypersensitivity reactions in humans and that lidocaine has an inhibitory effect on substance P-induced reactions.
 ...
PMID:Substance p-induced cutaneous and bronchial reactions in children with bronchial asthma. 170 91

Calcitonin gene-related peptide (CGRP) was injected alone and in combination with substance P (SP) or neurokinin A (NKA) into the forearm skin and temporal muscle of human volunteers. In the skin, 50 pmol of CGRP induced a wheal response and a delayed erythema. No pain was recorded. No interaction between CGRP and SP or NKA was observed. In the temporal muscle, 200 pmol of CGRP alone did not induce pain or tenderness but, in combination with SP or NKA, CGRP elicited a significant pain sensation. It is concluded that CGRP may be involved in neurogenic inflammation and that only SP, of the three peptides present in nociceptive C fibers, seems to be of major importance in relation to cutaneous nociception. Simultaneous neurogenic release of CGRP and other neuropeptides in skeletal muscle may induce myofascial pain.
 ...
PMID:Calcitonin gene-related peptide, neurokinin A and substance P: effects on nociception and neurogenic inflammation in human skin and temporal muscle. 171 69

Two non-sulfur containing ACE-inhibitors were tested concerning their local effect on experimental dermatitis in ovalbumin-sensitized guinea pigs. Enalaprilat but not cilazaprilat potentiated the ovalbumin-evoked inflammatory response. Furthermore, enalaprilat clearly enhanced the erythema evoked by substance P, whereas cilazaprilat did not. Concerning, the bradykinin-evoked erythema, enalaprilat significantly potentiated the response, whereas cilazaprilat only caused a slight increase. Our results suggest that different affinities for peptidases involved in degradation of inflammatory peptides can explain differences between the pro-inflammatory properties of enalaprilat and cilazaprilat.
 ...
PMID:Effects of cilazaprilat and enalaprilat on experimental dermatitis in guinea pigs. 171 14

Systemic capsaicin pretreatment (total cumulative dose 50 mg/kg administered s.c. over 2h) was performed in pigs under pentobarbitone anaesthesia and the effects on sensory and sympatho-adrenal mechanisms were examined acutely and 2 days after treatment. During pretreatment with capsaicin, pronounced sensory and sympatho-adrenal activation were noticed. This resulted in a several-fold increase in the systemic arterial plasma levels of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), noradrenaline (NA), adrenaline (Adr) and neuropeptide Y (NPY), and a slight increase (39%) in plasma cortisol. Simultaneously, there was marked tachycardia, an increase in blood pressure, total skin erythema and some bronchoconstriction, all lasting for about 30 min. Upon repeated injections tachyphylaxis was observed. 2 days after capsaicin pretreatment, basal plasma levels of the neuropeptides, catecholamines and cortisol as well as basal cardiovascular and pulmonary parameters were similar in control and capsaicin-treated pigs. The tissue content of CGRP and NKA was reduced by 50-65% in the airways and by 80-90% in the skin 2 days after capsaicin pretreatment. In contrast, the CGRP content was unchanged or increased (by 195%) in the nodose and spinal ganglia, respectively. The corresponding tissue levels of vasoactive intestinal polypeptide (VIP) and NPY were basically unchanged in capsaicin-treated pigs. A bolus injection of capsaicin (1 mg/kg i.v.) in control animals resulted in a marked increase in plasma catecholamines and NPY, concomitant with elevation in blood pressure and heart rate. These effects were preceded by an initial bradycardia and decrease in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Capsaicin-induced local effector responses, autonomic reflexes and sensory neuropeptide depletion in the pig. 185 42

Calcitonin gene-related peptide (CGRP) produced a dose-related wheal and flare reaction in human skin at doses of 12.5 to 50 pmol. The flare response but not the wheal response to CGRP and substance P were inhibited by prior treatment of the subject with oral chlorpheniramine, 16 mg. CGRP, but not substance P, was potent in producing a delayed erythema and surrounding pallor in human skin, which peaked at 1 h and persisted for more than 3 h after injection, when wheal and flare responses had subsided. The delayed response was accompanied by infiltration of polymorphonuclear leukocytes. The delayed erythema and pallor produced in response to CGRP were not inhibited by oral chlorpheniramine, or by 4% prilocaine injected locally. CGRP released histamine from rat peritoneal mast cells over the concentration range 2.5-10 microM. CGRP was about fourfold less potent than substance P in releasing histamine. The substance P analogue, [D-Pro4, D-Trp7,9,10]SP4-11 10 microM, and benzalkonium chloride 10 microM inhibited histamine release from rat mast cells stimulated by either CGRP or substance P.
 ...
PMID:Some effects of calcitonin gene-related peptide in human skin and on histamine release. 241 14

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.
 ...
PMID:Potent vasodilator activity of calcitonin gene-related peptide in human skin. 242 85

The effects evoked by intradermal injections of substance P (SP), neurokinin A (NKA) or calcitonin gene-related peptide (CGRP) were studied in 51 non-atopic subjects. SP and NKA produced flare and weal, and CGRP produced an indurated erythema. The reactions to SP were strong, the flare being maximal 3-5 min after injection and the weal after 10-15 min. NKA evoked a much weaker flare and a slightly weaker weal than did SP. CGRP produced a prominent long-lasting, indurated erythema with pseudopodia surrounded by a pallor edge. The mode of action of the three peptides was studied by pretreatment of the skin with the histamine-releasing compound 48/80, the H1-antagonist mepyramine or the local anesthetic xylocaine. The results suggest that mast-cell histamine and an intact sensory nerve supply are essential for the flare response to both SP and NKA. The weal response to SP was somewhat reduced by pretreatment with either 48/80 or xylocaine. The weal response to NKA, however, did not seem to depend upon either mast cells or sensory nerve fibres. The erythema evoked by CGRP was not suppressed by pretreatment with xylocaine, compound 48/80 or mepyramine, suggesting a direct action of CGRP on the blood vessels. The interaction between SP and CGRP was studied in subjects receiving a low dose of CGRP and increasing doses of SP or a low dose of SP and increasing doses of CGRP. CGRP did not potentiate the SP-evoked flare and weal and SP did not seem to enhance the response to CGRP.
 ...
PMID:Effects of substance P, neurokinin A and calcitonin gene-related peptide in human skin and their involvement in sensory nerve-mediated responses. 244 92

1 Neuropeptides released from sensory nerves may account for cutaneous flare and wheal following local trauma. In 28 normal subjects we have studied the effects of four sensory neuropeptides given by intradermal injection on the forearm or back. 2 All peptides caused a flare distant from the site of injection, presumably due to an axon reflex. Substance P (SP) was the most potent (geometric mean dose causing 50% of maximum flare, 4.2 pmol). Neurokinin A (NKA) was the next most potent with neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) the least. The distant flare response to SP, NKA and NKB was maximal at 5 min and disappeared within 2 h. 3 CGRP caused a local erythema over the site of injection at doses above 0.5 pmol which at higher doses lasted for up to 12 h. 4 SP, NKA and NKB caused wheals at doses above 5 pmol with SP and NKB being the most potent. CGRP (up to 250 pmol) did not consistently cause wheal formation. There was no significant effect of coinjection of CGRP upon the response to SP although there was a tendency for an enhancement of the wheal response. 5 The H1-histamine antagonist terfenadine (60 mg orally) significantly inhibited the wheal and distant flare response to histamine (5 nmol) and NKA, but not that caused by NKB. The distant flare of CGRP was also reduced but the local erythema was unaltered. 6. Aspirin (600 mg orally) significantly inhibited the distant flare response to SP, NKA and CGRP, but not that caused by NKB or histamine; the local erythema induced by CGRP was unaffected by aspirin. Aspirin also inhibited the wheal formed by NKA but not the wheal induced by the other substances. 7. These results suggest that tachykinins cause a distant flare response partially via the release of histamine and cyclo-oxygenase products, but cause a wheal by a direct effect on the skin microvasculature. The order of potency SP > NKB > NKA suggests that an SPp or NK, receptor is involved in the wheal response. CGRP by contrast has a direct vasodilator effect which is very prolonged.
 ...
PMID:Sensory neuropeptide effects in human skin. 289 55


1 2 3 4 Next >>