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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intrinsic nerve stimulation on the spontaneous electrical activity of the smooth muscle cells of the guinea pig ureter still attached to its renal pelvis were investigated using standard intracellular microelectrode techniques. Action potentials discharged spontaneously at a frequency of 3.3 +/- 0.2 min(-1) (n = 67) and consisted of an initial rapidly rising spike, followed by a variable period (0.2-5 s) of membrane potential oscillation and a quiescent plateau phase which was terminated by an abrupt repolarisation and after-hyperpolarisation to -66 mV. Transmural electrical stimulation (20-50 Hz for 2 s) transiently decreased the frequency of action potential discharge; the half-amplitude duration of the following action potentials, however, was transiently increased to 156 +/- 12% of control. Substance P (1 microM applied for 2 min) or neurokinin A (100 nM for 2 min) transiently increased the frequency of action potential discharge to 155 +/- 19% and 142 +/- 21%, respectively, of control. The excitatory actions of nerve stimulation or agonist application were reduced by the tachykinin antagonist, MEN 10,627 (1-3 microM), while the inhibitory actions of nerve stimulation were enhanced by MEN 10,627 (1 microM) or thiorphan (1 microM). Capsaicin (10 microM for 10-15 min) also evoked a transient increase in the frequency and half-amplitude duration of the ureteric action potentials, in a manner blocked by MEN 10,627 (3 microM), which was followed by a long period of membrane potential quiescence. Human calcitonin gene related peptide (hCGRP) (100 nM applied for 2-5 min) induced a time-dependent decrease in the frequency amplitude and duration of the spontaneous action potentials, in a manner blocked by glibenclamide (1 microM). It was concluded that the nerve-evoked excitatory and inhibitory changes in the parameters of the spontaneous ureteric action potentials arise from the release of the sensory neuropeptides, tachykinins and CGRP, respectively.
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PMID:Effects of nerve stimulation on spontaneously active preparations of the guinea pig ureter. 1055 May 20

We have tested the effect of the gap junction inhibitor, 18beta-glycyrrhetinic acid (18betaGA) on electromechanical coupling in the guinea-pig renal pelvis and ureter by the sucrose gap technique. In the ureter 18betaGA (3 - 30 microM) produced a concentration-dependent inhibition of the spike component of the action potential (AP) and reduced contraction evoked by electrical stimulation. Neurokinin A (NKA) produced a slow depolarization with superimposed APs and phasic contractions of the ureter. 18betaGA (30 microM) markedly inhibited the depolarization and APs evoked by NKA. However the contractile response was more sustained in the presence than in the absence of 18betaGA. At 100 microM, 18betaGA inhibited the mechanical responses to NKA. KCl (80 mM) produced APs and phasic contractions followed by sustained depolarization and tonic contraction. At 30 microM 18betaGA markedly inhibited the KCl-evoked APs and phasic contractions without affecting the sustained responses. At 100 microM 18betaGA inhibited the tonic contraction to KCl. In the renal pelvis 18betaGA (30 microM) inhibited the amplitude of pacemaker potentials and accompanying contractions and induced the appearance of low-amplitude APs not associated with contraction. We conclude that, up to 30 microM, the action of 18betaGA is consistent with an inhibition of cell-to-cell electrical coupling via gap junctions. The single-unit character of smooth muscles in the guinea-pig upper urinary tract is partly converted to a multi-unit pattern. At high concentrations 18betaGA possesses non specific effects which limit its usefulness as a tool for studying the role of gap junctions in smooth muscles. British Journal of Pharmacology (2000) 129, 163 - 169
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PMID:Effect of 18beta-glycyrrhetinic acid on electromechanical coupling in the guinea-pig renal pelvis and ureter. 1069 16

Non-steroidal anti-inflammatory drugs (NSAIDs) are currently considered a first-line treatment of renal colic. Their action has been ascribed to the inhibition of renal prostaglandin synthesis, which decreases renal blood flow and diuresis, and consequently lowers the pressure in the renal pelvis and ureter. However, the effects of NSAIDs on induced contractions of ureteral smooth muscle have received little attention. Also, there is a lack of clinically relevant spasmolytic drugs for the ureter. Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter. Serotonin (0.1-30 microM), norepinephrine (0.1-30 microM) and neurokinin A (0.03-10 microM) induced reproducible concentration-dependent contractions, which were inhibited by diclofenac and NS-398 (10-300 microM) in a concentration-dependent manner. The sensitivity of neurokinin A-induced contractions to diclofenac was 3-4 times greater than that of the amines. Depending on the concentration, inhibition ranged between 25 and 96% of the initially induced contractile activity. In the presence of inhibitors, supramaximal concentrations of agonists were unable to trigger recuperation of the initially induced contractions. Prostaglandin F2alpha did not reverse the effect of diclofenac on agonist-induced contractions. Removal of diclofenac or NS-398 from the organ baths showed that the inhibition was totally reversible. Thus, the non-selective COX inhibitor diclofenac and the selective COX-2 inhibitor NS-398 are almost equipotent in reducing agonist-induced contractions in the isolated porcine ureter. Although the clinical relevance of this spasmolytic effect remains to be demonstrated, the data suggest that patients suffering from renal colic may benefit not only from the anti-diuretic and analgesic effects of diclofenac, but also from its potential spasmolytic properties. Moreover, selective COX-2 inhibitors may have clinical potential, as they may cause fewer side effects.
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PMID:Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. 1122 16

The current study was designed to characterize the functionally active tachykinin receptors involved in tachykinin-elicited contractions in the pig intravesical ureter, and to investigate the possible modulation exerted by the natural tachykinins substance P (SP) and neurokinin A (NKA) on the non-adrenergic non-cholinergic (NANC) excitatory ureteral neurotransmission. In pig intravesical ureteral strips pretreated with phosphoramidon (10(-5) mol/L) to block the endopeptidase activities, isometric force recordings showed that SP, NKA, and the NK2 receptor selective agonist [beta-Ala(8)]-NKA (4-10), all three induced contractions, with the following potency order: NKA > [beta-Ala(8) ]-NKA (4-10) > SP. [Sar(9), Met(O(2))(11)]-SP and senktide, selective agonists of the NK1 and NK3 receptors, respectively, failed to modify the ureteral tone. Urothelium removal and incubation with tetrodotoxin (10(-6) mol/L), phentolamine (10(-7) mol/L), propranolol (3 x 10(-6) mol/L), atropine (10(-7) mol/L) and indomethacin (3 x 10(-6) mol/L), did not alter the contraction induced by a submaximal (10(-7) mol/L) dose of [beta-Ala(8)]-NKA (4-10). MEN 10,376 (10(-8)-10(-7) mol/L), a NK2 receptor antagonist, reduced the contraction to 3 x 10(-8) mol/L NKA. GR 82334 (10(-6) -10(-5) mol/L) and SR 142801 (10(-8)-10(-7) mol/L), selective antagonists of the NK1 and NK3 receptors, respectively, did not modify that contraction. In pig intravesical ureteral strips in NANC conditions, SP and NKA induced a potentiation of the contractions to electrical field stimulation (EFS) and to exogenous ATP. The results suggest that the tachykinins evoke a direct contraction of pig intravesical ureteral strips through NK2 receptors located in the smooth muscle. SP and NKA exert an enhancement of the NANC excitatory neurotransmission of the pig intravesical ureter.
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PMID:NK2 tachykinin receptors mediate contraction of the pig intravesical ureter: tachykinin-induced enhancement of non-adrenergic non-cholinergic excitatory neurotransmission. 1138 96

The presence, distribution and colocalisation of pituitary adenylate cyclase activating peptide (PACAP) immunoreactivity have been studied in the duck ureter by using Western blot analysis, radioimmunoassays (RIA) and immunohistochemistry. The presence of both PACAP-38 and PACAP-27 was demonstrated, PACAP-38 being the predominant form. PACAP-immunoreactive fibres and neurons were found in all the ureteral layers. Double immunostaining showed that PACAP was almost completely colocalised with vasoactive intestinal peptide (VIP). Moreover, PACAP was found in substance P (SP)-containing ureteral nerve fibres and in SP-containing dorsal root ganglion neurons. RIA performed on denervated ureters demonstrated that almost half of the ureteral PACAP was extrinsic in origin. These findings suggest that, in birds, PACAP has a role in diverse nerve-mediated ureteral functions.
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PMID:Pituitary adenylate cyclase activating peptide (PACAP) immunoreactivity in the ureter of the duck. 1157 87

The distribution and regional variation of nerves immunoreactive for the neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal polypeptide were investigated in the urinary bladder and distal ureter of young adult (3 months) and aged (24 months) male Wistar rats by indirect immunohistochemistry. Semi-quantitative estimations of nerve densities were made of peptidergic fibres innervating the dome, body and base of the urinary bladder and distal ureter. Sensory innervation of the dome was very sparse and the overall density of innervation increased progressively towards the base of the bladder. The density of innervation in the aged rats was closely comparable to that in the young adults, with the exception of slight reductions in CGRP and SP innervation of the muscle layer. Moreover, there was a marked reduction in the density of PACAP innervation of the subepithelial plexus and of the muscle layer of the bladder base. However, radioimmunoassay showed no significant difference (P>0.05) in PACAP contents between young and aged rat urinary bladder. In the distal ureter of aged rats the densities of innervation by fibres immunoreactive for SP and PACAP but not CGRP were reduced. These findings suggest that the level of sensory innervation of the bladder and distal ureter are reduced in old age and that the afferent limb of voiding reflexes may in consequence be perturbed.
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PMID:Distribution and regional variation of pituitary adenylate cyclase activating polypeptide and other neuropeptides in the rat urinary bladder and ureter: effects of age. 1220 43

The role of the autonomic innervation of the upper urinary tract for pyeloureteral motility is not completely understood. It is still debatable if the autonomic nervous system might play a modulating role on the ureteral peristalsis. The aim of this study was to investigate the distribution and regional variation of the intramural innervation using whole-mount preparations of the rabbit upper urinary tract. Whole-mount preparation was performed at upper urinary tracts of healthy rabbits. Immunohistochemistry was employed using Neurofilament (NF), Tyrosine Hydroxylase (TH), Choline Acetyltransferase (ChAT) and Substance P (SP) antibodies. NADPH-diaphorase and Acetylcholinesterase (AChE) histochemistry was carried out at the specimens. The stains were evaluated using brightfield, fluorescence and laser confocal microscopy. NF-, TH-, ChAT- and SP-immunoreactive (-IR) nerves formed distinct neuronal plexuses at the submucosal and muscle layers. Perivascular TH-, ChAT- and SP-IR fibres were demonstrated. AChE positive nerves were revealed in all layers, but only moderate NADPH-diaphorase positive innervation was found. Renal pelvis, upper and lower ureter showed enriched intrinsic innervation. Ganglia were found at the ureteropelvic border and the distal ureter. Whole-mount preparation technique revealed detailed informations about morphology and regional variation of the intramural innervation of the rabbit upper urinary tract.
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PMID:The intramural innervation of the rabbit upper urinary tract. 1287 43

The dorsal column pathway consists of direct projections from primary afferents and of ascending fibers of the post-synaptic dorsal column (PSDC) cells. This pathway mediates touch but may also mediate allodynia after nerve injury. The role of PSDC neurons in nerve injury-induced mechanical allodynia is unknown. Repetitive gentle, tactile stimulus or noxious pinch was applied to the ipsilateral hindpaw of rats with spinal nerve ligation (SNL) or sham surgery that had previously received tetramethylrhodamine dextran in the ipsilateral n. gracilis. Both touch and noxious stimuli produced marked increases in FOS expression in other cells throughout all laminae of the ipsilateral dorsal horn after nerve injury. However, virtually none of the identified PSDC cells expressed FOS immunofluorescence in response to repetitive touch or pinch in either the nerve-injured or sham groups. In contrast, labeled PSDC cells expressed FOS in response to ureter ligation and labeled spinothalamic tract (STT) cells expressed FOS in response to noxious pinch. Identified PSDC neurons from either sham-operated or SNL rats did not express immunoreactivity to substance P, CGRP, NPY, PKCY, MOR, the NK1 and the NPY-Y1 receptor. Retrogradely labeled DRG cells of nerve injured rats were large diameter neurons, which expressed NPY, but no detectable CGRP or substance P. Spinal nerve injury sensitizes neurons in the spinal dorsal horn to repetitive light touch but PSDC neurons apparently do not participate in touch-evoked allodynia. Sensitization of these non-PSDC neurons may result in activation of projections integral to the spinal/supraspinal processing of enhanced pain states and of descending facilitation, thus priming the central nervous system to interpret tactile stimuli as being aversive.
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PMID:Nerve injury-induced tactile allodynia is present in the absence of FOS labeling in retrogradely labeled post-synaptic dorsal column neurons. 1715 21

The effects of strepozotocin (STZ)-induced diabetes on the spontaneous peristaltic contractions in the upper urinary tract (UUT) of the rat were examined by simultaneously recording the tension in the proximal and distal regions of the renal pelvis and the proximal ureter. All regions of the UUT of diabetic rats contracted at a frequency similar to the contraction frequency of age-matched control rats. In contrast, contraction amplitudes in the proximal and distal renal pelvis and ureter of diabetic rats were 36%, 135% and 121% larger than the equivalent contractions recorded in control rats resulting in a significant increases in the motility index (MI amplitude x frequency) in all 3 regions. Capsaicin (10 microM), substance P (SP 2 microM) and neurokinin A (NKA 2 microM) caused a transient increase in MI in both control and STZ-induced diabetic rats. The rise in basal tension in the proximal and distal renal pelvis evoked by capsaicin, SP or NKA was also significantly greater in the diabetic rats when compared with controls. In contrast, human calcitonin-gene related peptide (hCGRP) produced a relatively small transient inhibition of UUT motility which was little affected by STZ treatment. These results suggest that capsaicin predominantly releases tachykinins from intrinsic sensory nerves in both non-diabetic and STZ-induced diabetic rats. We speculate that the supersensitivity of the diabetic UUT to capsaicin, NKA and SP 8-10 weeks after STZ treatment could be arising from an earlier development of sensory neuropathy.
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PMID:Pelviureteric peristaltic contractions in diabetic rats. 1792 48

This MiniReview focuses on the role played by nitric oxide (NO) and hydrogen sulfide (H2 S) in physiology of the upper and lower urinary tract. NO and H2 S, together with carbon monoxide, belong to the group of gaseous autocrine/paracrine messengers or gasotransmitters, which are employed for intra- and intercellular communication in almost all organ systems. Because they are lipid-soluble gases, gaseous transmitters are not constrained by cellular membranes, so that their storage in vesicles for later release is not possible. Gasotransmitter signals are terminated by falling concentrations upon reduction in production that are caused by reacting with cellular components (essentially reactive oxygen species and NO), binding to cellular components or diffusing away. NO and, more recently, H2 S have been identified as key mediators in neurotransmission of the urinary tract, involved in the regulation of ureteral smooth muscle activity and urinary flow ureteral resistance, as well as by playing a crucial role in the smooth muscle relaxation of bladder outlet region. Urinary bladder function is also dependent on integration of inhibitory mediators, such as NO, released from the urothelium. In the bladder base and distal ureter, the co-localization of neuronal NO synthase with substance P and calcitonin gene-related peptide in sensory nerves as well as the existence of a high nicotinamide adenine dinucleotide phosphate-diaphorase activity in dorsal root ganglion neurons also suggests the involvement of NO as a sensory neurotransmitter.
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PMID:The Role of Nitric Oxide and Hydrogen Sulfide in Urinary Tract Function. 2686 22


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