Biomedical subjects

Francisco Cruz

Publications and source records attributed to Francisco Cruz.

At least 19 recordsLinked to original sources

PubMed2006

TRPV1: a therapeutic target for novel analgesic drugs?

The vanilloid receptor TRPV1 is now recognized as a molecular integrator of painful stimuli ranging from noxious heat to endovanilloids in inflammation. Pharmacological blockade of TRPV1 represents a new strategy in pain relief. TRPV1 antagonists are expected to prevent pain by silencing receptors where pain is generated rather than stopping the propagation of pain, as most-traditional pain killers do. This hypothesis has already being tested in the clinic by administering small molecule TRPV1 antagonists (e.g. GlaxoSmithKline SB-705498) for migraine and dental pain. Paradoxically, in some murine models of chronic pain, TRPV1-deficient mice exhibit more pain-related behavior than their wild-type littermates, indicating that the understanding of TRPV1 in pain is still incomplete. Moreover, there is mounting evidence to suggest the existence of functional TRPV1 both in the brain and in various non-neuronal tissues. The biological role of these receptors remains elusive, but their tissue distribution clearly indicates that they are involved in many more functions than just pain perception. Here, we review the potential therapeutic indications and adverse effects of TRPV1 antagonists.

Analgesics↗

PubMed2006

TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications.

The transient receptor potential vanilloid subfamily 1 (TRPV1) is an ion channel activated by capsaicin, heat, protons and endogenous ligands such as anandamide. It is largely expressed in the urinary tract of mammals. Structures in which the receptor expression is firmly established include sensory fibers and urothelial cells, although the presence of TRPV1 in other cell types has been reported. As in other systems, pain perception was the first role attributed to TRPV1 in the urinary tract. However, it is now increasingly clear that TRPV1 also regulates the frequency of bladder reflex contractions, either through direct excitation of sensory fibers or through urothelial-sensory fiber cross talk involving the release of neuromediators from the epithelial cells. In addition, the recent identification of the receptor in urothelial and prostatic cancer cells raise the exciting hypothesis that TRPV1 is involved in cell differentiation. Desensitization of the receptor by capsaicin and resiniferatoxin has been investigated for therapeutic purposes. For the moment, lower urinary tract dysfunctions in which some benefit was obtained include painful bladder syndrome and overactive bladder of neurogenic and non-neurogenic origin. However, desensitization may become obsolete when non-toxic, potent TRPV1 antagonists become available.

Animals↗

PubMed2006

Interaction of iron-sulfur flavoprotein with oxygen and hydrogen peroxide.

The dimeric iron-sulfur flavoprotein (Isf) from Methanosarcina thermophila contains one 4Fe-4S center and one FMN per monomer, and is the prototype of a family widely distributed among strictly anaerobic prokaryotes. Although Isf is able to oxidize ferredoxin, the physiological electron acceptor is unknown; thus, the ability of Isf to reduce O2 and H2O2 was investigated. The product of O2 or H2O2 reduction by Isf was determined to be water. The kinetic parameters of the oxidative half-reactions with O2 and H2O2 as electron acceptors were consistent with a role for Isf in combating oxidative stress. Isf depleted of the 4Fe-4S cluster was unable to oxidize ferredoxin and reduce the FMN cofactor, supporting a role for the cluster in transfer of electrons from ferredoxin to the cofactor. The implications of these properties on the possible function and mechanism of Isf are discussed.

Electrons↗

PubMed2006

Spinal ERK activation contributes to the regulation of bladder function in spinal cord injured rats.

The extracellular signal-regulated kinase 1 and 2 (ERK) pathway, regulated by phosphorylation on specific amino acids, is emerging as an important signaling cascade in neurones, transducing sensory input into cellular responses. In the mammalian nervous system, the ERK pathway has been found to mediate plasticity events. Particularly, in the spinal cord, ERK play an important role in allodynia and hyperalgesia. Recently, it was demonstrated that ERK activation is upregulated in the spinal cord of rats with chronic bladder inflammation and contributes to bladder overactivity. Thus, in this study we sought to assess the involvement of ERK in micturition reflexes associated to spinal cord injury (SCI) in the rat. Bladder function in chronic SCI rats was altered compared to spinal intact rats. PhosphoERK levels were upregulated in the L6 spinal cord segment, particularly after saline infusion for 2 h. The increase in spinal ERK phosphorylation was specifically restricted to L6 spinal segment. No variation in the levels of total ERK protein was observed. Intrathecal administration of PD98059, a specific inhibitor of ERK phosphorylation, reduced the frequency and amplitude of bladder contractions in SCI animals but not in spinal intact ones. Overall, our results demonstrate increased activation of the ERK pathway in the spinal cord from SCI rats, restricted to spinal segments that receive sensory input arising from the bladder. Since the use of PD98059 reduced the frequency and amplitude of bladder contractions, ERK inhibitors may provide a new therapeutic approach to the treatment of bladder overactivity after spinal injuries.

Animals↗

PubMed2006

Junctional adhesion molecule-A regulates cell migration and resistance to shear stress.

Junctional adhesion molecule-A (JAM-A) is an adhesive protein expressed in endothelial cells, epithelial cells, platelets, and some leukocytes. JAM-A localizes to the tight junctions between contacting endothelial and epithelial cells, where it contributes to cell-cell adhesion and to the control of paracellular permeability. JAM-A also regulates cell motility, even though the quantitative biophysical features have not been characterized. In this study, we evaluated the role of JAM-A in the regulation of cell motility using JAM-A-expressing and JAM-A-deficient murine endothelial cells. We report that, in the absence of shear stress, JAM-A absence increases cell motility by increasing directional persistence but not cell speed. In addition, in the presence of shear stress, JAM-A absence increases protrusion extension in the direction of flow and increased downstream cellular displacement (while, conversely, decreasing upstream displacement). All these effects of JAM-A absence are mitigated by the microtubule-stabilizing compound taxol. A motility- and microtubule-related function, integrin-mediated adhesiveness, was only slightly reduced in JAM-A-deficient cells compared with JAM-A-expressing cells. However, overexpression of JAM-A in the JAM-A-deficient cells increased integrin adhesiveness to the same levels as those observed in taxol-treated JAM-A-deficient cells. Taken together, these data indicate that JAM-A regulates cell motility by cooperating with microtubule-stabilizing pathways.

Animals↗

PubMed2006

Engaging needles: a simple technique for arthroscopic side-to-side rotator cuff repair.

We propose that the tibial remnant of the anterior cruciate ligament (ACL) is able to enhance the revascularization and cellular proliferation of the graft, to preserve proprioceptive function, and to acquire anatomic placement of the graft without roof impingement. Therefore, it seems reasonable to assume that preserving the tibial remnant as much as possible as a source of reinnervation, if technically possible without causing impingement, would be of potential benefit to the patient. Our surgical technique was developed to maximize the preservation of the tibial remnant. The distally attached semitendinosus and gracilis tendons are harvested using a tendon stripper. Once satisfactory placement of 2 guide pins convergently is done, create a closed-end socket in the lateral femoral condyle with an adequate sized curved curette. For anatomic placement of the graft, the tibial tunnel should be positioned within the boundaries of the normal ACL tibial remnant. The reamer must be advanced very carefully to minimize injury to the residual remnant at the intra-articular margin of the tibial tunnel. Penetration should stop at the base of the stump. The folded grafts are then pulled intra-articularly through the tibial tunnel, the tibial remnant, and the femoral socket by pulling sutures under arthroscopic visualization. The ACL tibial remnant is compacted by the tendon passage. The graft is secured proximally by tying sutures in the lateral femoral condyle and distally at the tibia with double staples using a belt-buckle method. The advantages of our technique include maximal preservation of the tibial remnant, no roof impingement from intrasynovial anatomic placement of the graft, the simplicity of the procedure, the minimal need for hardware or special instruments, the economic benefit, and the potential prevention of tibial tunnel enlargement by preventing synovial fluid leakage.

Anesthesia, General↗

PubMed2006

Simple arthroscopic technique for rotator interval closure.

The rotator interval is a recognized source of pathology; there are several different techniques described for its closure but all require special instruments and skills. We present a technique that is simple in terms of skills and instrumentation. Two spinal needles are used. One needle is used as a suture retriever and the other as a suture passer. Each needle is passed through the margins of the rotator interval and, under arthroscopic vision, the needles are approximated to pass and retrieve the suture. Several sutures can be used as required. The knots are finally tied in an outside-inside fashion. This technique allows the surgeon to efficiently close the rotator interval under direct arthroscopic visualization in a few steps. The technique of arthroscopic rotator interval closure is simple, inexpensive, and easily reproducible.

Arthroscopy↗

PubMed2006

Engaging needles: a simple technique for arthroscopic side-to-side rotator cuff repair.

We present a simplified technique for the side-to-side arthroscopic rotator cuff repair. The instruments required for this technique are a 45 degrees Suture Lasso (SL; Arthrex, Naples, FL) and a 17F spinal needle (SN). With the arthroscope in the lateral portal, the SL is inserted through the posterior cannulas to grab healthy tissue at the posterior margin of the cuff. Through the anterior cannulas or through a skin puncture, the SN is inserted to catch healthy tissue at the anterior margin. Once both instruments are through the tissues, we manipulate them to make their tips converge. Because the SN diameter is small, it is very easy to engage its tip into the SL tip. Once engaged, a No. 1 PDS monofilament suture is easily passed through both instruments. When the suture comes out of the SL handle, both instruments can be pulled out, leaving the suture in place. Using a suture retriever clamp, the sutures are retrieved through a cannula for knot tying. This technique can be repeated as many times as necessary to place enough sutures in a side-to-side fashion to achieve the repair.

Arthroscopy↗

PubMed2006

Quality of life of rural menopausal women in response to a customized exercise programme.

AIM: This paper reports a study examining the effects of physical exercise on the quality of life of menopausal women. BACKGROUND: People who perform no type of physical activity have poorer physical and mental health. Despite the well-documented benefits of exercise, ageing women remain largely sedentary, and interventions designed to help them to maintain exercise programmes may prove particularly valuable. Measures should focus on increasing women's confidence so that they can overcome barriers to exercise. Conflicting results have been reported in intervention studies to promote exercise in postmenopausal women. METHODS: Forty-eight menopausal women aged 55-72 years were recruited at a primary care centre as voluntary participants in a quasi-experimental study. They were randomly assigned to one of two groups: control (n = 24) and experimental (n = 24). The experimental group participated in a 12-month programme of cardiorespiratory, stretching, muscle-strengthening and relaxation exercises carried out during two fully supervised exercise sessions per week (total of 3 hours weekly). Health-related quality of life was assessed by using the Quality of Life Profile for Chronically Ill Patients, a generic questionnaire widely used in epidemiological and clinical studies to measure well-being and function, incorporating as an optional module the Kupperman Index of Menopausal Symptomatology. RESULTS: There was a statistically significant improvement in the health-related quality of life of the experimental group, whereas the health-related quality of life of the control group significantly worsened. Menopausal symptoms also significantly improved in the experimental group and significantly worsened in the control group over the 12-month study period. CONCLUSIONS: A customized exercise programme is valuable for improving the health-related quality of life of menopausal women.

Aged↗

PubMed2005

[Pathological characteristics of thyroid microcarcinoma. A review of 402 biopsies].

BACKGROUND: Thyroid microcarcinoma is a tumor of 10 mm or less, that should have a low risk of mortality. However, a subgroup of these carcinomas is as aggressive as bigger tumors. AIM: To describe the pathological presentation of these tumors, and compare them with larger tumors. MATERIAL AND METHODS: All pathological samples of thyroid carcinoma that were obtained between 1992 and 2003, were studied. In all biopsies, the pathological type, tumor size, the focal or multifocal character, the presence of lymph node involvement and the presence of lymphocytic thyroiditis or thyroid hyperplasia, were recorded. RESULTS: One hundred eighteen microcarcinomas and 284 larger tumors were studied. The mean age of patients with microcarcinoma and larger tumors was 42.7+/-14 and 49.3+/-16 years respectively (p <0,001) and 83% were female, without gender differences between tumor types. Mean size of microcarcinomas was 8.6 mm and 116 (98%) were papillary carcinomas. Of these, 109 (94%) were well differentiated and seven (6%) were moderately differentiated. Thirty six (31%) were multifocal and in 10 (8,6%), there was lymph node involvement. The mean size of larger tumors was 23.8 mm and 241 (85%) were papillary carcinomas. Of these, 200 (83%) were well differentiated, and 41 (17%) were moderately differentiated. Eighty five (35%) were multifocal and in 44 (18%) there was lymph node involvement. The prevalence of thyroiditis and hyperplasia was significantly higher among microcarcinomas than in larger tumors (15 and 2.5%, respectively, p <0.001, for the former; 32.4 and 1.7%, respectively, p <0.001, for the latter). CONCLUSIONS: In this series, one third of microcarcinomas were multifocal and 10% had lymph node involvement. Therefore, the aggressiveness of these tumors is higher than what is reported in the literature and they should be treated with total thyroidectomy.

Adult↗

PubMed2005

The distribution of sensory fibers immunoreactive for the TRPV1 (capsaicin) receptor in the human prostate.

OBJECTIVES: To determine the distribution of sensory fibers immunoreactive to the pain receptor TRPV1 in the human prostate. METHODS: Eight prostates were harvested from cadaver transplant donors and immediately immersion fixed. Longitudinal and transverse 20 microm sections were cut on a cryostat and immunoreacted with two anti-human TPRV1 antibodies. RESULTS: TRPV1-immunoreactive nerve fibers were distributed throughout the prostatic urethral mucosa, verumontanum, ejaculatory ducts and periurethral prostatic acini. In the urethral mucosa, TRPV1-immunoreactive fibers penetrated the epithelial layer up to its surface. In the transitional and peripheral zones of the gland no TRPV1-immunoreactive nerve fibers were detected. CONCLUSIONS: The existence of a rich TRPV1 sensory innervation in the human prostate may open new therapeutic perspectives for the treatment of pain in patients with chronic prostatitis (Chronic Pelvic Pain Syndrome).

Antibodies↗

PubMed2005

Urodynamic effect of intravesical resiniferatoxin in patients with neurogenic detrusor overactivity of spinal origin: results of a double-blind randomized placebo-controlled trial.

OBJECTIVES: To access by a placebo-controlled randomized clinical trial the effect of intravesical resiniferatoxin on the urodynamic parameters of patients with neurogenic detrusor overactivity (NDO) of spinal origin. METHODS: Twenty eight patients with spinal NDO were randomised to receive intravesically 50 nM resiniferatoxin dissolved in 10% ethanol in saline (RTX group) or only the vehicle solution (placebo group). Filling cystometries were obtained in each patient at 1 month and 1 week before and at 1 and 3 months after treatment. In a visual analog scale patients were asked to estimate the discomfort induced by treatment. Patients were also persuaded to fill a micturition chart during the 3 days preceding each cystometry. RESULTS: The RTX and placebo groups were homogeneous in what respects the volume to first involuntary detrusor contraction (FDC, 143+/-95 ml and 115+/-58 ml, respectively, p=0.3) and maximal cystometric capacity (MCC, 189+/-99 ml and 198+/-111 ml, respectively, p=0.8). At the end of the study, mean FDC and MCC in the RTX group, 184+/-93 ml and 314+/-135 ml, respectively were significantly higher than in the placebo group, 115+/-61 ml (p=0.03) and 204+/-92 ml (p=0.02). In the visual analogue scale discomfort caused by treatment was similar. Only 10 patients in the RTX group and 6 patients in the placebo group completed adequately the micturition chart. Mean frequency and urinary incontinence decreased significantly only in the RTX group. CONCLUSIONS: Intravesical RTX is effective in increasing bladder capacity in spinal NDO patients. Such increment might contribute to decrease urinary frequency and incontinence of these patients.

Administration, Intravesical↗

PubMed2005

Inhibition of ERK phosphorylation decreases nociceptive behaviour in monoarthritic rats.

In this study we investigated the role of the activation of the extracellular signal-regulated kinases 1 and 2 (ERK) in chronic inflammatory articular nociception. Monoarthritis was induced in the left ankle of Wistar rats by injection of complete Freund's adjuvant (CFA). Movement of the inflamed joint increased ERK phosphorylation in neurones of the superficial and deep ipislateral dorsal horn laminae of L3-L5 spinal cord segments. Spinal immunoreactivity to phosphoERK was more intense in animals in which the inflammation lasted longer, 7 days or more, than in rats with less time of inflammation. PhosphoERK levels were transient, since 2h after ankle stimulation spinal immunoreaction had almost disappeared. PhosphoERK immunoreactivity was not induced by movement of ankles from non-arthritic control animals, neither in monoarthritic rats in which the inflamed ankle was not stimulated. Intrathecal administration of PD 98059, an inhibitor of ERK phosphorylation, reduced nociceptive behaviour induced by the ankle bend test in monoarthritic rats. The anti-nociceptive effect of PD 98059 was more prominent and in animals with short lasting (4 days) than in animals with longer (14 days) monoarthritis. Taken together, these findings suggest that ERK phosphorylation in spinal cord neurones plays an important role in chronic inflammatory articular pain and that its inhibition may provide significant anti-nociception.

Animals↗

PubMed2005

Increased spinal cord phosphorylation of extracellular signal-regulated kinases mediates micturition overactivity in rats with chronic bladder inflammation.

Spinal processing of somatosensory and viscerosensory information is greatly facilitated in some persistent pain states. Growing evidence suggests that the so-called central sensitization depends in part on intracellular activation and signalling via specific MAP kinases. Here we studied the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (phosphoERK), the active form of these kinases, in spinal neurons following innocuous and noxious distension of non-inflamed and cyclophosphamide (CYP)-inflamed rat urinary bladders. Additionally, we investigated the nature of bladder primary afferents responsible for spinal ERK activation. Finally, we used a specific inhibitor of ERK phosphorylation to study the influence of these kinases on the bladder reflex activity of normal and inflamed bladders. Results indicated that, in non-inflamed rats, noxious but not innocuous bladder distension significantly increased spinal phosphoERK immunoreactivity from its normal very low level. However, in CYP-inflamed rats, innocuous and noxious bladder distension significantly increased the number of spinal neurons immunoreactive to phosphoERK. ERK activation was rapid (within minutes) and transient. Desensitization of vanilloid-sensitive afferents by intravesical resiniferatoxin, a capsaicin analogue, did not decrease phosphoERK immunoreactivity in normal or CYP-inflamed rats. ERK inhibition by intrathecal PD 98059 had no effect on bladder reflex contractions of non-inflamed bladders but significantly decreased its frequency in inflamed animals. Our results suggest that spinal ERK intervene in acute and chronic inflammatory pain perception and mediate bladder reflex overactivity accompanying chronic bladder inflammation. In addition, bladder noxious input conveyed in vanilloid-resistant primary afferents is important to spinal ERK phosphorylation in both noninflamed and CYP-inflamed animals.

Animals↗

PubMed2005

Structures of the iron-sulfur flavoproteins from Methanosarcina thermophila and Archaeoglobus fulgidus.

Iron-sulfur flavoproteins (ISF) constitute a widespread family of redox-active proteins in anaerobic prokaryotes. Based on sequence homologies, their overall structure is expected to be similar to that of flavodoxins, but in addition to a flavin mononucleotide cofactor they also contain a cubane-type [4Fe:4S] cluster. In order to gain further insight into the function and properties of ISF, the three-dimensional structures of two ISF homologs, one from the thermophilic methanogen Methanosarcina thermophila and one from the hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus, were determined. The structures indicate that ISF assembles to form a tetramer and that electron transfer between the two types of redox cofactors requires oligomerization to juxtapose the flavin mononucleotide and [4Fe:4S] cluster bound to different subunits. This is only possible between different monomers upon oligomerization. Fundamental differences in the surface properties of the two ISF homologs underscore the diversity encountered within this protein family.

Amino Acid Sequence↗

PubMed2004

Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis.

The role of anandamide in the development of inflammatory hyperalgesia and visceral hyperreflexia was studied in the rat urinary bladder. Animals were given intraperitoneal cyclophosphamide injection, which evokes painful hemorrhagic cystitis accompanied by increased bladder reflex activity. The vanilloid receptor 1 [transient receptor potential vanilloid 1 (TRPV1)] antagonist capsazepine, applied onto the serosal surface of bladders, significantly reduced the hyperreflexia. Mass spectrometric analysis revealed that cyclophosphamide injection significantly and persistently increased the anandamide content of bladder tissues. The increase in the anandamide content paralleled the development of reflex hyperactivity. Anandamide (1-100 microm), applied onto the serosal surface of naive bladders, increased the reflex activity in a concentration-dependent manner. Repeated anandamide applications did not produce desensitization of the response. The anandamide-evoked effect was blocked by capsazepine or by instillation of resiniferatoxin, the ultrapotent TRPV1 agonist, into the bladders 24 hr before the anandamide challenge. The cannabinoid 1 receptor antagonist SR141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] significantly increased the potency of anandamide in enhancing bladder reflex activity in naive but not in cyclophosphamide-injected animals. Application of the fatty acid amide hydrolyze inhibitor palmitoylisopropylamine onto the serosal surface of bladders also increased the reflex activity both in naive and cyclophosphamide-injected rats. This latter effect in naive animals was blocked by capsazepine and by resiniferatoxin pretreatment. Finally, intravesical instillation of anandamide (50 microm) increased c-fos expression in the spinal cord, which was reduced by capsazepine or by resiniferatoxin pretreatment. These results suggest that anandamide, through activating TRPV1, contributes to the development of hyperreflexia and hyperalgesia during cystitis.

Acrolein↗

PubMed2004

Bladder C-fiber desensitization induces a long-lasting improvement of BPH-associated storage LUTS: a pilot study.

OBJECTIVES: To evaluate the effect of bladder C-fiber desensitization on BPH-associated storage LUTS. METHODS: Twelve patients with predominant BPH-associated storage LUTS gave written informed consent to enter the study. IPSS and QoL scores, micturition chart, uroflowmetry, cystometry and post-void residual (PVR) were obtained at baseline and at 1, 3 and 6 months after a single intravesical administration of 50 nM resiniferatoxin (RTX) solution. RESULTS: Mean IPSS score decreased from 20.1 +/- 6.0 to 10.5 +/- 4.4 at 1 month (p = 0.0001), to 10.3 +/- 4.4 at 3 months (p = 0.00001) and to 9.8 +/- 5.7 at 6 months (p < 0.00001). Mean QoL score decreased from 4.5 +/- 1 to 2.5 +/- 1 at 1 month (p = 0.0001), to 2.3 +/- 1 at 3 months (p = 0.0004) and to 2.6 +/- 1.2 at 6 months (p = 0.0003). Mean urinary frequency decreased from 15.2 +/- 8.5 to 10.8 +/- 7.3 at 1 month (p = 0.0002), to 10.2 +/- 4.9 at 3 months (p = 0.002) and to 11.7 +/- 9.2 at 6 months (p = 0.005). Urge incontinence, which was present in six cases, disappeared in 4 patients and decreased to less than half in the other two. Mean first desire to void and maximal cystometric capacity increased significantly after RTX whereas uroflowmetry and PVR were not altered. CONCLUSIONS: Intravesical desensitization of bladder C fibres with intravesical RTX might be useful in the treatment of patients with predominant BPH associated storage LUTS.

Aged↗

PubMed2004

Mechanisms involved in new therapies for overactive bladder.

During the last few years, vanilloid substances and botulinum-A toxin were extensively investigated as new therapies for overactive bladder. Intravesical administration of capsaicin or resiniferatoxin--2 members of the vanilloid family--has been shown to increase bladder capacity and decrease urge incontinence in patients with neurogenic, as well as nonneurogenic, forms of detrusor overactivity. In addition, vanilloids have been shown also to reduce bladder pain in patients with hypersensitive disorders. Vanilloids are exogenous ligands of vanilloid receptor type 1 (VR1), an ion channel present in the membrane of type C primary afferent nerve fibers. This receptor, which plays a key role in pain perception and control of the micturition reflex, may be upregulated by nerve growth factor (NGF), a neurotrophic molecule detected in high concentrations in overactive detrusor tissue. Vanilloids, by reducing uptake of NGF through sensory neurons, may counteract VR1 upregulation. Intravesical injections of botulinum-A toxin, a neurotoxin produced by Clostridium botulinum, were shown to increase bladder capacity and to decrease urge incontinence episodes in patients with neurogenic detrusor overactivity. Botulinum-A toxin impedes the release of acetylcholine from cholinergic nerve endings at the neuromuscular junction, leading to paralysis of the detrusor smooth muscle.

Animals↗