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)

1. Intravenous administration of three mammalian tachykinins (substance P, neurokinin A and neurokinin B) and three non-mammalian tachykinins (physalaemin, eledoisin and kassinin) induced dose-dependent increases in vascular permeability, as measured by Evans blue leakage technique, in various segments of the lower urinary tract (bladder dome and neck, proximal urethra, ureters) in urethane-anaesthetized rats. 2. Plasma extravasation induced by substance P (3.71 nmol kg-1 i.v.) was unaffected by pretreatment with antihistaminic drugs or methysergide. 3. A comparison of the relative potencies of various tachykinins did not allow characterization of a distinct type of receptor involved in the increase in vascular permeability. 4. The effects of tachykinin-related peptides which are selective agonists at the NK-1 (substance P-methylester, [Pro9]-SP-sulphone), NK-2 receptor [( Nle10]-NKA(4-10] or NK-3 receptor [( MePhe7]-NKB(4-10) and Senktide) indicated that NK-1 agonists are effective in the whole lower urinary tract, while NK-2 or NK-3 agonists are inactive or weakly active. 5. [beta-Ala4, Sar9]-SP(4-11)-sulphone, a selective NK-1 receptor agonist devoid of histamine-releasing properties, was highly potent and effective in producing plasma extravasation in the rat lower urinary tract. 6. These findings indicate that NK-1 receptors mediate the effect of intravenous tachykinins on vascular permeability in the rat lower urinary tract, through a histamine-independent mechanism.
 ...
PMID:Effects of tachykinins and selective tachykinin receptor agonists on vascular permeability in the rat lower urinary tract: evidence for the involvement of NK-1 receptors. 247 7

Either intra-arterial or topical administration of calcitonin gene-related peptide (CGRP) had little effect on motility of the urinary bladder in urethane-anaesthetized rats. Only a high concentration (50 microM) of topical CGRP activated the micturition reflex and potentiated the response to exogenous substance P (SP). In the isolated rat bladder CGRP had inconsistent effects on spontaneous or field-stimulated contractions. CGRP neither produced any significant plasma extravasation (Evans blue leakage) in the rat lower urinary tract, nor potentiated the response to exogenous SP. CGRP inhibited motility in the rat isolated proximal urethra and ureters and counteracted the contractile response to neurokinins. An inhibitory effect of capsaicin on stimulated motility of the urethra was observed in all preparations and a small contractile response was evident in about 40% of cases. Lack of desensitization to the action of CGRP prevented the study of its interaction with capsaicin. The inhibitory effect of CGRP in the ureter exhibited a specific desensitization: if the preparations were pre-exposed to exogenous CGRP, the inhibition of motility produced by antidromic activation of the capsaicin-sensitive nerve terminals (field stimulation) as well as the response to capsaicin (1 microM) was prevented but the inhibitory response to isoprenaline was unaffected. These findings indicate that CGRP is able to influence markedly the motility of the rat lower urinary tract, but exhibits marked regional differences in its action. Endogenous CGRP could be the inhibitory transmitter which, when released from capsaicin-sensitive fibers, participate in the control of ureteral motility.
 ...
PMID:Visceromotor responses to calcitonin gene-related peptide (CGRP) in the rat lower urinary tract: evidence for a transmitter role in the capsaicin-sensitive nerves of the ureter. 282 87

The detrusor muscle, bladder neck, proximal, middle and distal regions of the urethra of the female pig were studied by histochemical and immunohistochemical methods to localize catecholamine-containing, acetylcholinesterase-positive and peptide-containing nerves. The peptides examined included: vasoactive intestinal polypeptide, substance P, somatostatin, [Met]enkephalin, bombesin and gastrin. The greatest density of nerves was found in the smooth muscle of the distal urethra, followed by the bladder neck, middle urethra, and proximal urethra, with the least in the detrusor muscle. The greatest number of nerve fibres stained for acetylcholinesterase, followed by vasoactive intestinal polypeptide- and catecholamine-containing fibres. Substance P-immunoreactive nerve fibres were confined to the bladder neck and distal urethral regions. [Met]enkephalin-and gastrin-immunoreactive nerves were most dense in the distal urethra but absent in detrusor muscle, while somatostatin-immunoreactive nerve fibres were sparsely distributed throughout the lower urinary tract. No nerve fibres showing immunoreactivity to bombesin were found. Catecholamine-containing, acetylcholinesterase-positive, vasoactive intestinal polypeptide-, substance P-, [Met]enkephalin- and gastrin-immunoreactive nerves were also found on the adventitial-medial border of blood vessels in the pig urinary tract. In the intrinsic external urethral sphincter, located in the distal urethra, vasoactive intestinal polypeptide- and gastrin-immunoreactive nerve fibres were found bordering a small number of individual striated muscle fibres, while catecholamine-containing nerves were found predominantly in the connective tissue surrounding the striated muscle fibres. Dense populations of acetylcholinesterase-positive nerve fibres were found associated with the striated muscle fibres, with end plates on some of them. Intramural ganglia, composed of two to 30 neurones, were found in the bladder neck and middle and distal regions of the urethra. In the smooth muscle, and in the vicinity of the striated muscle regions of the intrinsic external urethral sphincter, there were small ganglia, containing two to three neurones, which were vasoactive intestinal polypeptide-, [Met]enkephalin- and somatostatin-immunoreactive. The results are compared to the autonomic innervation of the human bladder and urethra as previously described and it is concluded that the lower urinary tract of the pig is a good model for some features of the lower urinary tract of man, but a poor model for others.
 ...
PMID:A histochemical and immunohistochemical study of the autonomic innervation of the lower urinary tract of the female pig. Is the pig a good model for the human bladder and urethra? 291 69

Isolated urethral preparations from rabbit and man responded to transmural electrical stimulation with contraction when the basal tension was low, and with relaxation when the preparations were contracted by noradrenaline, clonidine, 5-hydroxytryptamine and lysine vasopressin. Both contractant and relaxant responses were abolished by tetrodotoxin, suggesting that they were caused by the action of transmitters released from nerves. The electrically induced contractions in the rabbit urethra had a threshold frequency of 5 to 6 Hz and maximum was reached at 40 Hz. The responses were markedly reduced by alpha-receptor blockers suggesting that the released contraction-mediating transmitter was mainly noradrenaline. The relaxant response was immediate and rapidly reversible. It was obtained at a threshold frequency of 1 to 2 Hz and maximum was reached at 10 to 15 Hz. It was not inhibited by propranolol, indomethacin, atropine or peptides such as substance P, VIP, vasopressin or somatostatin. Prostaglandin E2, isoprenaline, adenosine-5'-triphosphate and VIP relaxed the noradrenaline contracted rabbit urethra with a time course different from that of the electrically induced relaxation. Nifedipine and "calcium free" solution decreased the noradrenaline induced contraction but did not influence the relaxant response to electrical stimulation. It is suggested that the relaxant response of the isolated noradrenaline-contracted urethra to electrical stimulation is caused by an unknown transmitter released from nerves.
 ...
PMID:Electrically induced relaxation of the noradrenaline contracted isolated urethra from rabbit and man. 613 Nov 47

We studied the effects of a variety of noncholinergic, nonadrenergic agents on the smooth muscles of the cat urethra. Prostaglandin F2 alpha contracted both urethral muscle layers to a similar extent. Prostaglandin E2 contracted the longitudinal and relaxed the circular muscle layers. The effects of the prostaglandins seem to be directly myogenic since cholinergic and adrenergic blockers and tetrodotoxin did not affect them. Bradykinin and substance P contracted both urethral muscle layers. Other tested agonists (neurotensin, vasoactive intestinal peptide, cyclic 3,5 adenosine monophosphate, adenosine diphosphate sodium, cyclic 3,5 guanosine monophosphate sodium, bombesin) had no effect on the cat urethral smooth muscles.
 ...
PMID:Response of urethral smooth muscles to pharmacological agents. II. Noncholinergic, nonadrenergic agonists and antagonists. 619 58

The occurrence of neurogenic inflammation as indicated by Evans blue extravasation was studied in various organs of the guinea-pig. Electrical stimulation of the trigeminal nerve caused Evans blue extravasation due to increased vascular permeability in the nasal mucosa and gingiva. Vagal stimulation induced extravasation in the epiglottis, larynx, trachea, bronchial tree and esophagus. Splanchnic stimulation induced Evans blue extravasation in the gall bladder, bile ducts and superior mesenteric artery. Stimulation of the inferior mesenteric ganglion caused a marked extravasation in the upper and middle part of both ureters, while pelvic activation induced a reaction in the lower ureter, urinary bladder, urethra and vagina. I.v. substance P (SP) (3 nmol X kg11) or capsaicin (1 mumol X kg-1) both induced extravasation in many tissues including those in which nerve stimulation produced a response. The extravasation responses to SP, capsaicin or nerve stimulation all had similar border-line zones, such as esophagus to stomach, bile ducts to duodenum, rectum to anal mucosa, pulmonary artery to heart and vagina to uterus. Quantitative determinations showed especially large permeability effects in the trachea, umbilical ligament and ureter. The permeability effect of capsaicin and nerve stimulation was abolished in capsaicin-pretreated animals, while the response to SP was still present. Capsaicin pretreatment caused an almost total loss of SP in several visceral organs including the respiratory and urinary tracts. The SP content in these tissues was correlated (r = 0.97) to the Evans blue extravasation following nerve stimulation or i.v. capsaicin. SP and capsaicin caused contractions in vitro of the esophagus, ureter, urinary bladder, trachea and gall bladder. The capsaicin-induced contraction of the trachea was resistant to tetrodotoxin pretreatment. The non-cholinergic, non-adrenergic contraction of the urinary bladder upon field stimulation was still present in capsaicin-pretreated animals. In conclusion, neurogenic inflammation occurs in several organs with a highly region-specific distribution, which is accompanied by the presence of capsaicin-sensitive SP neurons. Both parasympathetic and sympathetic pathways contain capsaicin-sensitive afferent fibres which mediate an increase in vascular permeability most likely by releasing SP. In addition, both capsaicin and SP cause smooth muscle contraction in several visceral organs.
 ...
PMID:Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea-pig. 620 Oct 40

Following treatment of adult rats with nerve growth factor (0.5 mg/rat, three times a week for 3 weeks), the innervation of cardiovascular and urinogenital tract smooth muscle was investigated using immunoassay and immunohistochemical techniques. Substance P and calcitonin gene-related peptide levels were increased in the vas deferens, but not in the atria or femoral artery. Neuropeptide Y and vasoactive intestinal polypeptide levels were unchanged. In penile tissues, there was a marked increase in the density of substance P-, calcitonin gene-related peptide-, neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide-containing nerves innervating the urethra and in SP-containing nerves in the tunica with little changes in the innervation of the deep dorsal vein and artery and corpus cavernosum. In the bladder, there was increased innervation of the detrusor by neuropeptide Y- and vasoactive intestinal polypeptide-containing nerves, but a decrease in innervation by substance P-containing nerves in the trigone. There were no changes in the density of innervation of the femoral artery after nerve growth factor treatment. Thus, in the mature rat, sensory and sympathetic nerve innervating urinogenital tract smooth muscle appear to be more responsive to exogenous nerve growth factor than those innervating cardiovascular smooth muscle. This may reflect an ongoing requirement of plasticity of innervation in the urinogenital tract of the sexually mature animal.
 ...
PMID:Nerve growth factor treatment of adult rats selectively enhances innervation of urinogenital tract rather than vascular smooth muscle. 748 10

In the present study, the distribution of neuropeptides in the human penis is demonstrated by immunohistochemistry (IHC). IHC screening detected a complex network of nerve fibers containing vasoactive intestinal polypeptide (VIP), peptide histidine-methionine (PHM), prepro-VIP (111-122), neuropeptide Y (NPY), C-flanking peptide of NPY (C-PON), calcitonin gene-related peptide, substance P, and galanin immunoreactivities. Special attention was also given to the recently isolated, VIP-related lizard peptide helospectin, which could also be detected in neuronal elements in the penis. Colocalization studies showed the coexistence of VIP, PHM, and partly helospectin, and of NPY with C-PON within nerve fibers in the cavernous and spongious body, the glans penis, and the urethra.
 ...
PMID:Neuropeptides in the human penis: an immunohistochemical study. 753 24

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l-ENK-IR nerves together with a few m-ENK-IR nerves. Occasional smooth muscle-associated varicose nerve fibres showed immunoreactivity for SP, CGRP, VIP or BOM although the majority of these types of nerve formed perivascular plexuses. Also at 26 wk numerous varicose nerve fibres were observed in association with the prostatic acini, the majority of such nerves containing NPY with a few showing immunoreactivity to VIP, l-ENK, SP or CGRP.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Development of peptide-containing nerves in the human fetal prostate gland. 759 78

The distribution of NO synthase (NOS) immunoreactive nerves and the possible co-existence with other neurotransmitters were investigated in the pig lower urinary tract. NOS immunoreactive nerves were found in the muscle layer, in the lamina propria and around blood vessels. The density of NOS immunoreactive nerves was more prominent in the trigone and urethra than in the detrusor. All parts of the lower urinary tract were supplied by numerous acetylcholine esterase (AChE) positive nerves. The number of adrenergic nerves in the trigone and urethra was moderate to rich, whereas only very few adrenergic nerves were demonstrated in the detrusor. A low to moderate number of nerve fibres containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) were observed in the trigone and urethra, while very few were found in the detrusor. A small number of nerves, confined to the trigone and urethra, were stained for calcitonin-gene-related peptide, somatostatin and leu-enkephalin. Nerve fibres exhibiting immunoreactivity to bombesin/gastrin releasing peptide, gastrin/cholecystokinin, substance P or neurokinin A were virtually absent. Co-localization studies revealed that some NOS-immunoreactive nerves also stained for NPY, VIP or AChE. The present study shows that nitrergic nerves are present in the pig lower urinary tract in a density lower than the cholinergic, but higher than any of the studied peptidergic nerves. Coinciding localization of NOS-positive nerves with nerves expressing AChE, VIP and NPY suggests that NO may have a role as a messenger in the lower urinary tract directly and by interaction with other transmitters.
 ...
PMID:Co-existence of nitrergic, peptidergic and acetylcholine esterase-positive nerves in the pig lower urinary tract. 761


<< Previous 1 2 3 4 Next >>