Biomedical subjects

H Kumon

Publications and source records attributed to H Kumon.

At least 73 records · Page 4Linked to original sources

PubMed1998

Fosfomycin reduces CD15s-related antigen expression of Streptococcus pyogenes.

We have previously shown the immunological mimicry of human sialyl-Lewis(x) (CD15s) by a surface antigen of Streptococcus pyogenes. This mimicking surface antigen may act as a ligand to the selectin family and may induce antibody production against CD15s on host cells, suggesting a possible role in the pathogenesis of S. pyogenes. In this study, the effects of antibiotics on the CD15s-related antigen expression of S. pyogenes were examined at a concentration below the MIC (sub-MIC). The amounts of CD15s on the surfaces of S. pyogenes cells and on the surfaces of S. pyogenes biofilms were determined by a whole-cell enzyme-linked immunosorbent assay and by laser scanning fluorescence microscopy, respectively, by using an anti-CD15s monoclonal antibody. At the sub-MICs, fosfomycin (1R,2S-1,2-epoxypropyl phosphonic acid), its enantiomer (1S,2R-1,2-epoxypropyl phosphonic acid), and benzylpenicillin significantly inhibited the CD15s expression of all strains studied. The effects of fosfomycin and its enantiomer on biofilms were also observed by scanning electron microscopy. Incubation of S. pyogenes with the sub-MIC of fosfomycin or its enantiomer, which has no antibacterial activity, reduced the amount of CD15s on the biofilm surface and made it smooth. These results suggest that fosfomycin or its enantiomer might be useful for preventing S. pyogenes adherence to human CD15s receptors and the resulting immunological pathogenicity.

Anti-Bacterial Agents↗

PubMed1998

Absorption of epirubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer.

As postoperative adjuvant therapy for superficial bladder cancer, intravesical instillation therapy is commonly conducted. In this case, from the view point of prevention of intraoperative dissemination, commencement of instillation therapy at an early postoperative period is preferred. However, increased drug permeability is suspected because of damage to the bladder mucosa during operation. Therefore, this study was conducted to investigate the plasma level of epirubicin (EPI) instilled immediately after transurethral operation. EPI (20 mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral operation, and retained in the bladder for 1 h. Blood samples were obtained before instillation, as well as 30, 60, 120 and 240 min after instillation, and EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40 ml group (n = 5) were < 2.5 and < 2.0 at 30 and 60 min, respectively, after which they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and < 3.0 after 30, 60 and 120 min, respectively, and after 240 min it was undetectable. Intravesical instillation of EPI immediately after a transurethral operation causes a small increase in the plasma level and it is thought to cause small systemic side effects.

Absorption↗

PubMed1998

[Antimicrobial prophylaxis in transurethral resection of the prostate].

OBJECTIVE: A prospective trial was performed to propose a suitable antimicrobial prophylaxis in patients undergoing transurethral resection of the prostate (TUR-P). SUBJECTS AND METHODS: Patients who underwent TUR-P due to symptomatic prostatic hyperplasia between April 1995 and February 1996 were included. Based on the results of urinalysis obtained within preoperative 3 days, the patients were classified into Group I (less than 5 WBC/hpf and bacterial count of less than 10(4) CFU/ml in urine specimen), and Group II (5 or more WBC/hpf or bacterial count of 10(4) or more CFU/ml in urine specimen). Furthermore, each group was randomly subdivided into Group A and Group B according to the period of antimicrobial administration. As prophylactic antimicrobials, cefazolin (CEZ) was used in Group I and CEZ or cefotiam (CTM) in Group II. The antimicrobial was administered only on the day of operation in Group IA (n = 92), for 3 days in Group IB (n = 96), 2 days in Group IIA (n = 37), and 4 days in Group IIB (n = 30). On the day of operation, the antimicrobial was infused immediately before the operation. The presence or absence of pyuria, bacteriuria and febrile infection, and the period required for normalization of the urinalysis were the major points evaluated here. RESULTS: No significant differences were observed in any parameters with respect to the period of administration of antimicrobial between the groups, but in both Group I and Group II, the incidence of febrile infection was higher in the groups with shorter antimicrobial administration periods. The mean period for normalization of the urinalysis required 68.4, 68.6, 65.2 and 58.2 days in Group IA, Group IB, Group IIA and Group IIB, respectively. CONCLUSION: It is concluded that 3 or 4-day administration of first or second generation parenteral cephems is generally acceptable regimen for antimicrobial prophylaxis in patients undergoing TUR-P.

Aged↗

PubMed1998

[Combination chemotherapy with cis-platinum and ifosfamide for hormone unresponsive prostate cancer].

PURPOSE: There is no effective therapy against hormone refractory prostate cancer. This led us to evaluate the effectiveness and toxicity of cis-platinum (CDDP) and ifosfamide (IFM) combination chemotherapy in the patients with hormone-unresponsive carcinoma of the prostate. METHODS: Patients with hormone-unresponsive prostate cancer were scheduled to receive CDDP 70 mg/m2 intravenously on day 1 and IFM 1.2 g/m2/day intravenously on day 1 through day 5 of 28-day cycle. RESULTS: Twenty seven patients with hormone unresponsive prostate cancer were enrolled onto this trial. Of these patients, seven (26%) demonstrated a partial objective response (PR), and ten (37%) a stable disease (ST). The response duration of PR cases lasted from 6 to 49 months with a median of 16 months and the response duration of PR + ST cases lasted from 3 to 36 months with a median of 10 months. Subjective improvement was obtained in 11 patients (41%). Survival duration of all cases were 4 to 89 months with a median of 23 months and probabilities of survival at 3 years and 5 years were 36% and 24%, respectively. The toxicity of this treatment was mostly mild to moderate, anemia (96%), leukocytopenia (89%), anorexia (81%), alopecia (67%), thrombocytopenia (44%), hematuria (38%), renal dysfunction (19%) and liver dysfunction (7%) were noticed. Severe toxicity was observed in two cases, one acute renal failure and one endotoxin shock. CONCLUSION: We conclude that CDDP and IFM combination chemotherapy was active regimen for hormone unresponsive prostate cancer.

Aged↗

PubMed1998

High incidence of occult neurogenic bladder dysfunction in neurologically intact patients with thoracolumbar spinal injuries.

PURPOSE: We determine the relationship between lower urinary tract function and somatic neurological status after thoracolumbar fracture. MATERIALS AND METHODS: Within 72 hours of thoracolumbar vertebral fracture we evaluated 44 consecutive patients, including 30 men and 14 women 17 to 84 years old (mean age 38.7), with occult neurogenic bladder dysfunction following incomplete thoracolumbar spinal injuries (American Spinal Injury Association impairment classifications C to E). The neurological level and degree of injury were established, and testing for perianal pinprick sensation and bulbocavernosus reflex was done. Video urodynamic evaluation was then performed between 3 and 14 days after injury but before spinal surgery. RESULTS: Urodynamics revealed neurogenic lower urinary tract dysfunction in all 10 patients with classification C, 82% with D and 41% with E (otherwise completely intact neurologically) impairment. Although pinprick sensation deficiency and decreased bulbocavernosus reflex correlated with injury classification, lower urinary tract dysfunction was present in 62% of the patients with intact pinprick sensation and in 59% with intact bulbocavernosus reflex. CONCLUSIONS: Neurologically intact patients with thoracolumbar spinal injuries may have neurogenic lower urinary tract dysfunction on urodynamics. Pinprick sensation and bulbocavernosus reflex are specific but not sensitive indicators of lower urinary tract dysfunction after spinal cord injury. Although these indicators, which demonstrate somatic nerve function, were absent in all patients with detrusor areflexia, intact pinprick sensation and bulbocavernosus reflex are not sensitive for predicting lower urinary tract function, which depends on autonomic nerve function. Urodynamic evaluation is mandatory for the complete evaluation of patients with incomplete lumbosacral spinal injuries.

Adolescent↗

PubMed1998

[Chronic perianal pyoderma with urethrocutaneous fistula: a case report].

A 65-year-old male was hospitalized because of micturition pain and urinary oozing from several fistulas on the perineal and the left gluteal skin. Oozing had been present for about 50 years, after receiving mass resection of his left scrotum or perineum, and left orchiectomy. The main focus was on the left dorsal site of the anus. Compression around this area produced malodorous grayish pus discharge from many fistulas, although the anus was intact. Although he had histories of spinal caries and renal tuberculosis, both pus and urine cultures showed Staphylococcus spp. and no growth of Mycobacterium tuberculosis. Urethrocystography showed urethral stenosis at bulbar urethra and leakage from a site just proximal to the stenosis. Antibiotics for tuberculosis were administrated for fear of recurrent tuberculosis for 6 months. Cystostomy formation and debridement were performed, followed by en-bloc resection and mesh-skin graft after two weeks. Internal urethrotomy was performed six months after the surgery, and subsequently cystostomy removed. After three and a half years, although there was no local recurrence and no difficulty of urination, he died of cholangio-carcinoma. There are many reports of chronic perianal pyoderma subsequent to hemorrhoid or subcutaneous abscess; however, this might be the first report on a case originating from fistulas in the urinary tract.

Aged↗

PubMed1998

Ice-water test in the urodynamic evaluation of spinal cord injured patients.

The purpose of this study was to determine the clinical utility of the ice-water test (IWT) during urodynamic evaluation in spinal cord injured (SCI) patients. Thirty-two suprasacral SCI patients with documented detrusor hyperreflexia (DH) underwent urodynamic study and IWT. Fifteen patients had repeated testing 2 weeks later. The IWT was performed with the patient in the supine position; 100 mL of sterile saline water at 4-8 degrees C was injected manually. If cystometric capacity was <200 mL, a volume of about 50% of the individual cystometric bladder capacity was used. The cold fluid was left within the bladder for 3 minutes. The test was considered positive if an involuntary bladder contraction > or =15 cm H2O was registered. All patients with cervical or thoracic level SCI had DH, which had 100% test-retest reproducibility on urodynamics. Seventy-two percent of patients with DH had a positive IWT and 28% had a negative IWT. IWT (same volume, 2 weeks later) in 4 (27%) of the 15 repeated tests gave different responses. Autonomic hyperreflexia, manifested as systolic blood pressure increase > or =50 mm Hg within 3 minutes of ice-water instillation, occurred in 16 (57%) of 28 patients with lesions above T7. In SCI patients, the IWT did not contribute to their management because of the insensitivity and nonspecificity. Autonomic hyperreflexia can occur during evaluation. The IWT did not influence clinical management in this group of SCI patients.

Administration, Intravesical↗

PubMed1998

Development of noninvasive velocity flow video urodynamics using Doppler sonography. Part I: Experimental urethra.

PURPOSE: We believed that a totally noninvasive video urodynamic system could be invented based on the concept of Doppler ultrasonography. To develop this system we measured flow velocity in an experimental urethra using 4 materials, including natural urine. MATERIALS AND METHODS: A cellulose tube was inserted into a standoff pad as an experimental urethra. Degassed water, distilled water, urine and liposome (multi-lamellar particles) solution comprised the 4 materials used to compare signal intensity and flow velocity at various flow rates. The flow rate from the tube was measured with a uroflowmeter. The Doppler image and digital uroflow signal data were processed by a computer. RESULTS: Doppler signals and flow velocity curves could be sufficiently obtained using distilled water, urine and liposome solution, while degassed water showed no Doppler signals at any flow rate. Minimum flow rate at which clear Doppler signals were continuously detected from the angle in the frontal plane was greater than 3.0 ml. per second for distilled water, greater than 1.5 for urine and greater than 0.3 for liposome solution. Maximum flow velocities were identical in these 3 materials at a flow rate of greater than 2.0 ml. per second. The functional cross-sectional area of the tube showed a constant value irrelevant to the initial flow rate. CONCLUSIONS: Flow velocity could be measured by Doppler ultrasound above a certain minimal flow rate. Dissolved gasses have an important role in creating Doppler signals. Flow velocity, velocity related parameters and functional cross-sectional area can diagnose and localize the area of bladder outlet obstruction. Liposome solution may be helpful in detecting velocity in low flow states in future systems.

Contrast Media↗

PubMed1998

Development of noninvasive velocity flow video urodynamics using Doppler sonography. Part II: clinical application in bladder outlet obstruction.

OBJECTIVES: We have developed a totally noninvasive urodynamic technique based on the concept of Doppler sonography, which was tested in men with and without bladder outlet obstruction. MATERIALS AND METHODS: An ultrasonic image directed Doppler system with a 3.75 MHz. micro-convex electro-probe was operated transperineally using a specially devised remote control robotic holder. Uroflow rates from the urethral meatus were also measured with a flowmeter. The color Doppler ultrasound image and digital flow velocity data were processed by a personal computer. Color scale data were analyzed by customized software. Multiple rectangle sample volumes could be set in any size in any position, and the resulting color encoded data were averaged. Calculation was performed every 0.5 second and a flow velocity curve in the region of interest was obtained. A total of 12 men, 6 without (controls) and 6 with bladder outlet obstruction, were evaluated by conventional pressure flow study and the new Doppler ultrasound urodynamic system. Bladder outlet obstruction was determined using the nomogram of Abrams and Griffiths. The sample volume for a flow velocity curve was set only in the prostatic urethra and, thus, maximum flow velocity in and functional cross-sectional area of the prostatic urethra were determined. RESULTS: Urinary stream in the male urethra was clearly detected and flow velocity in the prostatic urethra could be measured in all cases. Maximum flow rate measured by a flowmeter was significantly lower in the bladder outlet obstruction group. Maximum flow velocity by Doppler study was almost the same in the obstructed and control groups. Functional cross-sectional area, which was calculated by dividing maximum flow rate by maximum flow velocity, was lower in the bladder outlet obstruction (mean plus or minus standard deviation 0.31+/-0.16 cm.2) than control group (0.78+/-0.23 cm.2) (p = 0.006). Velocity flow plots were possible in both groups. CONCLUSIONS: The concept of noninvasive pressure flow-like urodynamic evaluation based on Doppler ultrasound is feasible. Parameters of flow velocity as well as functional cross-sectional area can be used in the diagnosis of bladder outlet obstruction and to localize the site of obstruction.

Humans↗

PubMed1997

Vacuolar-type H(+)-ATPase in mouse bladder epithelium is responsible for urinary acidification.

The urine in the mouse bladder was found to be acidic, ranging from pH 5.3 to 5.5 in the daytime and pH 6.0 to 6.3 at night. Administration of bafilomycin A1 or concanamycin A, specific inhibitors of vacuolar-type H(+)-ATPase, into bladder lumen caused neutralization of urinary pH at least for 36 h, whereas inhibitors of mitochondrial ATP synthase (F-type H(+)-ATPase) or P-type H(+)-ATPases did not. Bafilomycin A1-sensitive proton secretion from isolated inside-out bladder was also observed. Immuno-electron microscopy with antibodies against vacuolar H(+)-ATPase revealed that vacuolar-type H(+)-ATPase is rich in luminal plasma membrane and endosomes of superficial cells of the bladder epithelium. These results indicate that vacuolar-type H(+)-ATPases present in luminal plasma membrane of the superficial epithelial cells secrete protons so as to acidify the urine in mouse bladder.

Animals↗

PubMed1997

Impact of 3-dimensional helical computerized tomography on selection of operative methods for ureteropelvic junction obstruction.

PURPOSE: We studied the feasibility of imaging the direct correlation between crossing vessels and obstructed ureteropelvic junction with helical (spiral) computerized tomography (CT) for selecting surgical repair of symptomatic ureteropelvic junction obstruction. MATERIALS AND METHODS: From July 1995 to December 1995, 4 select patients with symptomatic ureteropelvic junction obstruction underwent contrast enhanced helical CT. In addition to transaxial images, 3-dimensional reformatted images were used for evaluation. RESULTS: We identified 2 cases of ureteropelvic junction obstruction due to crossing vessels regarded as ureterovascular hydronephrosis, which is characterized by the spatial relationship between malrotated renal pelvis and anterior crossing vessels. Laparoscopic or open repair was performed in these 2 patients and operative findings were in agreement with prospective helical CT interpretation. Antegrade endopyelotomy was performed successfully for the remaining 2 patients. CONCLUSIONS: The 3-dimensional helical CT is reliable in detecting ureterovascular hydronephrosis preoperatively and in presenting better operative methods for ureteropelvic junction obstruction.

Adult↗

PubMed1997

Gracilis urethral myoplasty: preliminary experience using an autologous urinary sphincter for post-prostatectomy incontinence.

PURPOSE: We investigated the effect of a neurovascular intact gracilis muscle urethral wrap to restore urinary continence in men with severe stress urinary incontinence after radical retropubic prostatectomy. MATERIALS AND METHODS: Three men with stress incontinence after radical retropubic prostatectomy and external beam radiation therapy for adenocarcinoma of the prostate underwent gracilis urethral myoplasty. Video urodynamic evaluation and cystourethroscopy revealed Valsalva leak point pressure of less than 40 cm. water and a damaged urinary sphincter mechanism in all 3 patients. One man underwent concomitant ileocystoplasty. RESULTS: At 6 to 24-month followup all patients reported improved continence. Mean Valsalva leak point pressure increased from 26.3 +/- 3.2 cm. water before to 83.0 +/- 32.1 cm. water after surgery. The gracilis muscle urethral wrap did not have a deleterious effect on erectile function or ambulation. Complications included 1 wound infection. CONCLUSIONS: An autologous gracilis muscle urinary neosphincter can be constructed in the bulbous urethra in a fashion similar to that of the artificial urinary sphincter with encouraging results in this preliminary series. The gracilis neosphincter may be an alternative to the artificial sphincter, especially in patients at higher risk for complications, such as after radiation and cryotherapy.

Aged↗

PubMed1997

L-aspartate but not the D form is secreted through microvesicle-mediated exocytosis and is sequestered through Na+-dependent transporter in rat pinealocytes.

Rat pinealocytes accumulate glutamate in microvesicles and secrete it through exocytosis so as to transmit signals intercellularly. Glutamate is involved in the negative regulation of norepinephrine-stimulated melatonin production. In this study, we found that aspartate is also released from cultured rat pinealocytes during the exocytosis of glutamate. The release of aspartate was triggered by addition of KCI or A23187 (a Ca2+ ionophore) in the presence of Ca2+ and was proportional to the amount of L-glutamate released. Furthermore, the release of aspartate was inhibited by both botulinum neurotoxin type E and L- or N-type voltage-gated Ca2+ channel blockers. Bay K 8644, an agonist for the L-type Ca2+ channel, stimulated the release of aspartate 2.1-fold. Immunohistochemical analyses with antibodies against aspartate and synaptophysin revealed that aspartate is colocalized with synaptophysin in a cultured pinealocyte. HPLC with fluorometric detection indicated that the released aspartate is of the L form, although pinealocytes also contain the D form in their cytoplasm, corresponding to approximately 30% of the total free aspartate. Radiolabeled L-aspartate was taken up by the microsomal fraction from bovine pineal glands in a Na+-dependent manner. The Na+-dependent uptake of L-aspartate was strongly inhibited by L-cysteine sulfinate, beta-hydroxyaspartate, and L-serine-O-sulfate, inhibitors for the Na+-dependent glutamate/aspartate transporter on the plasma membrane. Na+-dependent sequestration of L-aspartate was also observed in cultured rat pinealocytes, which was inhibited similarly by these transporter inhibitors. These results strongly suggest that L-aspartate is released through microvesicle-mediated exocytosis from pinealocytes and is taken up again through the Na+-dependent transporter at the plasma membrane. The possible role of L-aspartate as an intercellular chemical transmitter in the pineal gland is discussed.

Amino Acid Transport System X-AG↗

PubMed1997

In-vivo whole bladder response to anticholinergic and musculotropic agents in spinal cord injured rats.

The purpose of this study was to compare the effect on urodynamic parameters of anticholinergic and musculotropic agents in sham injured and spinal cord injured (SCI) rats. A standard rat SCI model induced by impact trauma was employed. Cystometrograms were performed under urethane anesthesia four weeks after SCI. Bladder capacity and voiding pressure were determined at the point of micturition monitored urodynamically and visually. The effect of oxybutynin chloride (0.01-0.1 mg/kg), propantheline bromide (0.05-0.5 mg/kg) and flavoxate hydrochloride (0.1-1.0 mg/kg) were assessed independently in sham injured and SCI rats (n = 10 in each group). Bladder capacities were 0.6 +/- 0.2 and 7.1 +/- 1.6 ml in sham and SCI rats (p < 0.01), respectively. Maximal filling pressure was 17.5 +/- 5 mmHg in sham and 25 +/- 5 mmHg in SCI rats (p < 0.05). Bladder capacity increased with all three medications. Administration of oxybutynin, propantheline and flavoxate in sham rats resulted in bladder capacities of 0.88 +/- 0.3, 0.71 +/- 0.3 and 0.8 +/- 0.2 ml, respectively (p < 0.01). In SCI rats, these drugs resulted in bladder capacities of 9.8 +/- 1.1, 7.9 +/- 1.3 and 8.8 +/- 2.0 ml, respectively (p < 0.01). No significant change in maximum filling pressure occurred. We conclude that anticholinergic and musculotropic agents caused a similar increase in bladder capacity in both sham and SCI rats. Oxybutynin enhanced bladder capacity more than propantheline or flavoxate.

Animals↗

PubMed1997

Endoscopic correction of vesicoureteral reflux by subureteric Teflon (polytetrafluoroethylene) injection: review of 6-year experience.

BACKGROUND: Endoscopic correction of vesicoureteral reflux (VUR) was first proposed in 1981 and the first series of patients treated by subureteric polytetrafluoroethylene paste injection (STING) was reported in 1984. Although many successful studies, primarily European, have been undertaken since then, this technique has recently been rejected in the United States. In this paper, we report our 6-year experience and discuss indications for this technique. PATIENTS AND METHODS: Since February 1990, we have used the STING technique to endoscopically correct VUR. In this analysis, 38 ureters in 24 patients (mean age, 47.3 years; range, 7 to 79 years), with at least 1 year of follow-up were included. RESULTS: The first injection resulted in disappearance of VUR in 34 ureters (89.5%). A second injection was done for 2 failed and 3 recurrent ureters during follow-up, resulting in disappearance of VUR in the 3 recurrent ureters. The final success rates were 100% for both primary VUR and secondary VUR due to neurogenic bladder, but only 55.6% (5/9) for secondary VUR following transurethral resection of bladder tumors. No postoperative early or delayed complications were noted in any case. CONCLUSION: The procedure is simple and effective for the treatment of all grades of VUR. However, the procedure should be performed after careful consideration of the indications, since theoretically the risk of distant migration of the paste cannot be ignored.

Adolescent↗

PubMed1997

[Significance of rectal contractions during multichannel urodynamic study].

BACKGROUND: The influence of rectal contractions on urination was examined using multichannel urodynamic study. METHODS: We reviewed a total of 246 consecutive urodynamic studies. Each study consisted of a uroflow measurement and multi-channel urodynamic study, evaluating total vesical pressure, abdominal (rectal) pressure, subtracted detrusor pressure and perianal electromyography. Rectal contractions were defined as periodic fluctuations over 5 cmH2O in abdominal pressure detected by a rectal balloon catheter. No relationship of these contractions with cough and breathing was observed. RESULTS: Of the 246 patients, 17 (6.9%) had a positive study for rectal contractions. The patients, who had positive rectal contractions, averaged 70-year-old were older than negative subjects averaged 62-year-old. In multichannel urodynamics, the flow rate was significantly decreased, and electromyographic activity was increased at the moment of each rectal contractions. CONCLUSIONS: The rectal contractions are not artifactual and may be regarded as one of causes responsible for urinary difficulty in the elderly.

Adult↗

PubMed1996

Urologic manifestation of spinal cord sarcoidosis.

We present the first report of neurogenic lower urinary tract dysfunction associated with neurosarcoidosis. Urodynamic findings of detrusor hyperreflexia with detrusor-sphincter dyssynergia correlate with this patient's magnetic resonance imaging (MRI) examination which found intramedullary involvement at the mid-thoracic level.

Adult↗

PubMed1996

The L-type Ca2+ channel is involved in microvesicle-mediated glutamate exocytosis from rat pinealocytes.

Pinealocytes, parenchymal cells of the pineal gland, secrete glutamate through microvesicle-mediated exocytosis upon depolarization by KCl in the presence of Ca2+, which is involved in a novel paracrine-like intercellular signal transduction mechanism in neuroendocrine organs. In the present study, we investigated whether or not the L-type Ca2+ channel is involved in the microvesicle-mediated glutamate secretion from cultured rat pinealocytes. Nifedipine, a specific antagonist of the L-type Ca2+ channel, inhibited the Ca(2+)-dependent glutamate exocytosis by 48% at 20 microM. Other L-type Ca2+ channel antagonists, such as nitrendipine, showed similar effects. 1,4-Dihydro-2,6-dimethyl-5-nitro-4 [2-(trifluoromethyl)-phenyl]-3-pyridinecarboxylic acid methyl ester (BAY K8644), an agonist of the L-type Ca2+ channel, at 1 microM, on the other hand, stimulated the glutamate exocytosis about 1.6-fold. Consistently, these Ca2+ channel antagonists inhibited about 50% of the Ca2+ uptake, whereas BAY K8644 increased the uptake 5.3-fold. An antibody against the carboxyl-terminal region of the rabbit L-type Ca2+ channel recognized polypeptides of pinealocytes with apparent molecular masses of 250 and 270 kDa, respectively, and immunostained the plasma membrane region of the pinealocytes. These results strongly suggested that the entry of Ca2+ through L-type Ca2+ channel(s), at least in part, triggers microvesicle-mediated glutamate exocytosis in pinealocytes.

Animals↗