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. The tachykinin receptor mediating contraction of the guinea-pig isolated proximal urethra has been characterized by use of receptor selective agonists and antagonists. All experiments were performed in the presence of peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each) in order to reduce peptide degradation. 2. The natural tachykinins, substance P and neurokinin A produced a concentration-dependent contraction of rings of the proximal urethra which approached the same maximum (about 50% of the response to 80 mM KCl). Substance P (EC50 155 nM) was slightly (3.6 times) more potent than neurokinin A (EC50 560 nM). 3. The tachykinin NK1 receptor selective agonist, [Sar9]substance P sulphone (EC50 62 nM), was slightly more potent than substance P and produced the same maximal response of natural tachykinins. The NK2 receptor selective agonist, [beta Ala8] neurokinin A(4-10), was active only at microM concentrations and its maximal effect did not exceed 20% of that to substance P or neurokinin A. The NK3 receptor selective agonist, senktide, was ineffective up to 30 microM. 4. The response to [Sar9]substance P sulphone was antagonized in a competitive manner by either (+/-)-CP 96,345 (pA2 7.75, slope - 1.10) or GR 82,334 (pA2 7.31, slope - 1.26), which are selective NK1 receptor antagonists, while it was unaffected (up to 10 microM) by MEN 10,376, a selective NK2 receptor antagonist. 5. The response to 10 microM [beta Ala8]neurokinin A (4-10) was abolished by either 0.2 microM (+/-)-CP 96,345 or 1 microM GR 82,334, suggesting the involvement of NK1 receptors.6. Electrical field stimulation (5 and 10 Hz, 0.25 ms, 100 V, trains of 5 s duration) produced tetrodotoxin-sensitive phasic contractions of the urethra which were abolished by atropine plus phentolamine (3 microM each). Capsaicin (1 microM) produced a small transient contraction of the urethra which was abolished by ( )-CP 96,345 (0.1 microM). ( )-CP 96,345 did not modify the response to electrical field stimulation.7. We conclude that tachykinin NK, receptors are the main if not the only mediators of the contractile response of guinea-pig proximal urethra to peptides of this family and that this preparation is useful for assessing the affinities of various ligands for the NK, receptor. Endogenous tachykinins released from peripheral endings of capsaicin-sensitive primary afferents produce urethral contraction by activating NK, receptors.
 ...
PMID:Tachykinin NK1 receptor in the guinea-pig isolated proximal urethra: characterization by receptor selective agonists and antagonists. 132 90

The urinary bladder and urethral content of substance P and vasoactive intestinal polypeptide and the in vitro effects of the peptides on the bladder were studied at 6 weeks and 6 months of streptozotocin-induced diabetes in the rat. The results were compared with those obtained in age-matched control animals. Both short-term and long-term streptozotocin treatment induced a clearcut increase in bladder weight. Bladder substance P content was increased in both groups of diabetic animals but substance P concentration was similar in control and diabetic animals. Vasoactive intestinal polypeptide content was slightly higher in diabetic animals than in controls but vasoactive intestinal polypeptide concentration was significantly lower in the bladders from both short-term and long-term diabetic animals. The bladder contractile response to substance P was similar in all groups of animals and vasoactive intestinal polypeptide was found to be devoid of contractile or relaxatory effects in the rat bladder. No change in urethral weight was seen with diabetes. There were no clear-cut changes in the urethral contents or concentrations of substance P and vasoactive intestinal polypeptide. The study also enabled comparisons between younger (3 months) and older (9 months) rats. This comparison showed a decrease in the concentrations and contents of substance P and vasoactive intestinal polypeptide between young and older rats. The changes were seen in both the bladder and the urethra and were similar in diabetic and normal animals.
 ...
PMID:Effects of age and streptozotocin-induced diabetes on contents and effects of substance P and vasoactive intestinal polypeptide in the lower urinary tract of the rat. 137 98

The influence of muscle type on functional responses of the female rat urethra was investigated using morphological and functional in-vitro techniques. The urethral submucosa was found to contain longitudinally or obliquely oriented smooth muscle cells. The muscularis layer is composed of circularly oriented muscle cells. Near the bladder orifice smooth muscle fibres dominate, but in the mid-urethra the vast majority is circularly oriented striated muscle cells. Circular preparations responded to electrical field stimulation in vitro with a rapid contraction. Stimulation with single impulses resulted in a twitch response; frequencies exceeding 5-10 Hz induced a summation and tetanus. The response was unaffected by phenoxybenzamine, propranolol and scopolamine and had a low sensitivity to calcium-free solution but was sensitive to suxamethonium and tetrodotoxin. Using longer impulse trains stimulation evoked also a slow contraction, sensitive to calcium-free solution. In longitudinal preparations stimulation induced a relaxation followed by a contraction, responses much smaller than those seen in the circular preparations. Both preparations relaxed on addition of calcitonin gene-related peptide or capsaicin. The relaxation to calcitonin gene-related peptide was larger than that to capsaicin in longitudinal preparations but equally large in the circular ones. Substance P and 5-hydroxytryptamine contracted both preparations. The longitudinal urethra showed a larger contraction to 5-hydroxytryptamine than to substance P, whereas both substances induced similar responses in the circular preparations. The study shows a similar muscle arrangement in the female rat urethra as described in humans and further points to a functional differentiation between the different types of muscle.
 ...
PMID:Functional responses of different muscle types of the female rat urethra in vitro. 208 4

The contractile response to natural tachykinins [substance P (SP), neurokinin A (NKA), arginin-neurokinin B (ArgNKB)] and to synthetic peptide [Pro9]SP sulfone, [beta Ala8]NKA(4-10) and [MePhe7]NKB, were investigated in the isolated smooth muscle from the human prostatic urethra. Natural tachykinins evoked concentration-related responses with the following order of potency: NKA----NKB--------SP. Among selective agonists [beta Ala8]NKA(4-10) produced concentration-related contractions, while [Pro9]SP sulfone and [MePhe7]NKB were inactive. These data indicate the presence of NK-2 receptors in the smooth muscle of the human prostatic urethra.
 ...
PMID:The contractile effect of tachykinins on human prostatic urethra: involvement of NK-2 receptors. 217 70

The sensory innervation of the urinary bladder and urethra plays a key role in a variety of reflexes involved in urine storage and voiding. Dysfunction of these systems is a possible cause of many disturbances related to urine continence but basic knowledge in this field has been hampered by the lack of tools for studying sensory nerves. The use of capsaicin, the pungent ingredient of red peppers, allowed us to investigate the anatomical and functional properties of a specific subset of sensory neurons in the lower urinary tract. These 'capsaicin-sensitive' neurons play a dual sensory and 'efferent' function, determined by transmitter release from their central and peripheral nerve endings. Tachykinins, including substance P, and other neuropeptides such as calcitonin gene-related peptide, mediate the functions of these sensory neurons. The 'sensory' function includes regulation of micturition threshold, activation of cardiovascular reflexes and perception of pain from the urinary bladder. The 'efferent' function includes local regulation of muscle cell activity, nerve excitability, blood flow and plasma protein extravasation. Recent data suggest that capsaicin-sensitive sensory nerves could be present in the human bladder.
 ...
PMID:The dual function of capsaicin-sensitive sensory nerves in the bladder and urethra. 222 67

The urethral mucosa in the canine penis was immunostained by use of antibodies against substance P and calcitonin gene-related peptide. Numerous nerve fibers immunoreactive for both peptides were found to invade the epithelium from the tunica propria; here they ran various courses with occasional branchings and conspicuous varicosities. Some looped to return into the tunica propria, while others ended on the epithelial surface. These findings confirm and extend our knowledge on the sensory innervation of the urethra which has previously been based on silver impregnation techniques.
 ...
PMID:Nerve fibers in the urethral mucosa of canine penis are immunoreactive for both substance P and calcitonin gene-related peptide. 242 83

Specimens obtained by transurethral sphincterectomy from patients with spinal cord injury and carcinoma of the bladder were studied immunohistochemically. In the smooth muscle region of the sphincter, vasoactive intestinal polypeptide-, substance P- and somatostatin-immunoreactive fluorescent, varicose nerve fibers were seen. In the striated muscle region, VIP-immunoreactive nerves were found around striated muscle fibers and bundles, while somatostatin- and substance P-immunoreactive nerves were confined to nerve bundles. In both the smooth and striated muscle regions of the intrinsic external urethral sphincter, VIP-immunoreactive nerves were seen around blood vessels. No differences were observed in the immunohistochemical localization of these peptide-containing nerves in the two groups of patients. No immunofluorescence for [Met]enkephalin, bombesin, neurotensin or serotonin was found in any nerves in the urethra.
 ...
PMID:Vasoactive intestinal polypeptide-, somatostatin- and substance P-immunoreactive nerves in the smooth and striated muscle of the intrinsic external urethral sphincter of patients with spinal cord injury. 242 76

The innervation of rat and guinea pig urinary tract was examined using immunohistochemistry, radioimmunoassay and True Blue retrograde tracing techniques and was further assessed following both surgical and chemical denervation experiments. Substantial amounts of calcitonin gene-related peptide-like immunoreactivity (range 20-150 pmol/g) were detected in tissue extracts and localised to nerve fibres distributed throughout the urinary tract of both species, these being concentrated in the ureter and base of the bladder. In the guinea pig, the number and distribution pattern of calcitonin gene-related peptide-like immunoreactive nerves appeared to be identical to that of substance P-containing nerves, whereas in the rat the former predominated. Seven days after injection of the fluorescent dye True Blue into tissues of the urinary tract, retrogradely labelled cells were found in the dorsal root ganglia. These cells had a segmental distribution pattern which was specific for each of the injection sites. Thus, after injection of True Blue into the left kidney hilum a single group of labelled cells were found in the ipsilateral T10-L2 dorsal root ganglia. In contrast, injection into the left ureter produced labelled cells in two separate groups of ipsilateral ganglia (T11-L3 and L6-S1). Injection into the wall of the bladder and upper urethra resulted in bilateral labelling, with most labelled cells occurring in L6 and S1 ganglia. Approximately 90% of labelled cells in T10-L3 dorsal root ganglia displayed calcitonin gene-related peptide-like immunoreactivity, but only 60% of retrogradely labelled bladder neurons in L6-S1 ganglia were immunoreactive for this peptide. Adult guinea pigs and neonatal rats injected systemically with capsaicin subsequently exhibited a marked reduction both in the amount of calcitonin gene-related peptide immunostaining and the concentration of immunoreactive material in the urinary tract, dorsal root ganglia and spinal cord. In rats treated neonatally with capsaicin, there was a significant reduction in the number of retrogradely labelled cells and a hypertrophy of the bladder. Sectioning of the pelvic and hypogastric nerves in the rat also resulted in a depletion of calcitonin gene-related peptide-like immunoreactive nerves in the bladder, whereas chemical sympathectomy appeared to have no effect. The results indicate that calcitonin gene-related peptide immunoreactivity occurs in a major proportion of afferent neurons supplying the urinary tract of the rat and guinea pig.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: combined retrograde tracing and immunohistochemistry. 242 72

The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra. However, the maximal response to NKA was about twice that of SP on the urethra and bladder neck. Capsaicin did not affect motility of the unstimulated rat isolated ureter, while NKA or SP activated rhythmic contractions, NKA being about 850 times more potent than SP. Either capsaicin or field stimulation produced a transient inhibition of the NKA-activated rhythmic contractions of the rat isolated ureter which was prevented by capsaicin-desensitization. The capsaicin-(1 microM) or field stimulation-induced inhibition of NKA-activated rhythmic contractions of the rat isolated ureter were unaffected by removal of pelvic ganglia but abolished by cold storage (72 h at 4 degrees C). Intravenous capsaicin induced an inflammatory response (Evans blue leakage) in the bladder, proximal urethra and ureters in vivo. Plasma extravasation was greater in the ureters, urethra and bladder neck than in the dome. SP, NKA and histamine produced a dose-dependent dye leakage in all segments of the rat urinary tract, the response being slightly greater in the bladder neck than in the dome. The capsaicin-induced inflammatory response was abolished by systemic capsaicin-desensitization and reduced, to a variable extent, by pelvic ganglionectomy, in the various tissues examined. Topical application of tetrodotoxin on the bladder dome failed to affect the capsaicin-induced plasma extravasation in the urinary bladder. These findings indicate that chemoceptive, capsaicin-sensitive nerves are present throughout the whole rat lower urinary tract and their activation determines a variety of visceromotor responses and an increase of vascular permeability. In various instances the response to capsaicin may be explained by the action of tachykinins but some effects may involve other sensory neuropeptides.
 ...
PMID:Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract. 244 29

The effects of neurokinins (NKs), tachykinins and some NK-related peptides (selective agonists for the NK-1, NK-2 or NK-3 receptors) have been investigated in the various sections of the rat lower urinary tract. In the isolated bladder, all peptides were substantially equipotent with the exception of senktide, an NK-3 agonist, which was distinctly less potent than the other compounds. Similar results were obtained in the isolated urethra. In these tissues, the maximal response to NK-1 agonists was distinctly less intense than that to the other peptides. In the bladder, exposure to phenoxybenzamine (30 microM for 90 min) reduced the response to NK-A but not that to substance P, KCl or field stimulation. In the isolated ureter, peptides active at both the NK-2 and the NK-3 sites [including senktide and [MePhe7]-NKB(4-10)] activated, at nanomolar concentrations a series of rhythmic contractions, whereas peptides active at the NK-1 site, were active only at micromolar concentrations. These findings provide further evidence that multiple NK receptors are present in the rat lower urinary tract. In the bladder, NK-2 and NK-1 sites mediate the direct response to NKs, in accordance with binding and autoradiographic data. In the ureter, both NK-2 and NK-3 sites may activate the direct contractile response to these substances.
 ...
PMID:Neurokinin receptors in the rat lower urinary tract. 245 93


1 2 3 4 Next >>