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Biomedical subjects

W Kong

Publications and source records attributed to W Kong.

At least 19 recordsLinked to original sources
PubMed2006

Waiting times for cancer surgery in Ontario: 1984-2000.

AIMS: Despite persistent public interest and the perception among clinicians and patients that increased waiting time for cancer surgery is related to worse outcomes, little is known about waiting time for cancer surgery. Our aim is to describe changes in waiting times for cancer surgery in Ontario between 1984 and 2000, and associated factors. MATERIALS AND METHODS: The interval between date of diagnosis and admission for surgery for all patients receiving surgical treatment for cancers of the larynx, hypopharynx, stomach, colon, rectum, breast, cervix, uterus, prostate, bladder, lung and oesophagus was calculated for all patients in Ontario between 1984 and June 2000. This was accomplished by retrospective review of prospectively gathered electronic records. RESULTS: Median waiting times for cancer surgery increased for all cancer types, including substantial increases for oesophageal cancer (from 14 days between 1984 and 1987 to 33 days between 1998 and 2000), breast cancer (12-27 days), and laryngeal cancer (16-33 days). A similar increase in waiting times for patients awaiting radiation therapy was identified. The proportion of patients receiving diagnosis and definitive resection on the same admission for colon cancer decreased (from 79.4% between 1984 and 1987 to 47.9% between 1998 and 2000) for laryngeal cancer (35.5-9.4%), and for lung cancer (61.6-23.0%). Age, sex, cancer site, hospital type, household income and cancer centre location were all independently related to waiting times. CONCLUSIONS: Waiting times for cancer surgery increased substantially between 1984 and 2000. Waiting times were influenced by disease, patient and health-system-related factors.

Aged↗
PubMed2001

Development of a three-dimensional transmigration assay for testing cell--polymer interactions for tissue engineering applications.

The ability of synthetic or natural scaffolds to support invasion of cells from surrounding tissue is a key parameter for tissue engineering (TE). In this study, the migration of fibroblasts, chondrocytes, and osteoblasts into biodegradable polymer scaffolds was evaluated using a novel, three-dimensional (3-D) transmigration assay. This assay is based on a cell-populated contracted collagen lattice with a biodegradable polymer scaffold implanted at the center of the collagen gel. Cell migration into the scaffolds was assessed both quantitatively and qualitatively following various time lengths in culture using image analysis. Chondrocytes, incorporated within the collagen lattice, migrated into polymer scaffolds, when cultured both statically or in a rotating bioreactor. However, the bioreactor cultures resulted in a significantly greater cell invasion as compared to static cultures. There was a cell density-dependent osteoblast migration from collagen lattice into polymer scaffold, when tested in the transmigration assay. In addition, polymer scaffolds, treated with or without recombinant human platelet-derived growth factor (rh-PDGF-BB) were evaluated for fibroblast migration. The presence of rh-PDGF-BB resulted in significantly greater fibroblast invasion as compared to untreated scaffolds. Our studies suggest that the transmigration model provides a rapid system for testing cell invasion of potential scaffolds for tissue engineering applications.

Becaplermin↗
PubMed2001

Mechanism of alpha-adrenergic regulation of expressed hKv4.3 currents.

The transient outward potassium current (I(to)) is an important repolarizing current in the mammalian heart. I(to) is regulated by adrenergic stimulation; however, the effect of agonists on this current, and consequently the action potential duration and profile, is variable. An important source of the variability is the difference in the channel genes that underlie I(to). There are two subfamilies of candidate genes that are likely to encode I(to) in the mammalian heart: Kv4 and Kv1.4; the predominance of either gene is a function of the species, stage of development, and region of the heart. The existence of different isoforms of the Kv4 family (principally Kv4.2 or Kv4.3) further complicates the effect of alpha-adrenergic modulation of cardiac I(to). In the human ventricle, hKv4.3 is the predominant gene underlying I(to). Two splice variants of human Kv4.3 (hKv4.3) are present in the human ventricle; the longer splice variant contains a 19-amino acid insert in the COOH-terminus with a consensus protein kinase C (PKC) site. We used heterologous expression of hKv4.3 splice variants and studies of human ventricular myocytes to demonstrate that alpha-adrenergic modulation of I(to) occurs through a PKC signaling pathway and that only the long splice variant (hKv4.3-L) is modulated via this pathway. Only a single hKv4.3-L monomer in the tetrameric I(to) channel is required to confer sensitivity to phenylephrine (PE). Mutation of the PKC site in hKv4.3-L eliminates alpha-adrenergic modulation of the hKv4.3-encoded current. The similar, albeit less robust, modulation of human ventricular I(to) by PE suggests that hKv4.3-L is expressed in a functional form in the human heart.

Adrenergic alpha-Agonists↗
PubMed2001

[Chronic hypoxia altered the mRNA expression of cyclooxygenase in intrapulmonary artery smooth muscle cell].

OBJECTIVE: To elucidate the effect of chronic hypoxia on the cyclooxygenase-2 mRNA expression in pulmonary artery smooth muscle cells of rats. METHODS: The gene expressions of COX-1 and COX-2 during acute hypoxia were measured with semi-quantified RT-PCR in the 2nd, 4th and 6th subculture of intrapulmonary artery smooth muscle cells (PASMC) of wistar rats under normoxic and continuous hypoxic condition separately. RESULTS: In all three generations, the expressions of COX-1 had no significant changes in hypoxia, while the COX-2 mRNA expression was higher in chronic hypoxic group than that in normoxic group and elevated with the duration of hypoxia exposure. After exposure to acute hypoxia, the augmentation of COX-2 mRNA expression in PASMC was higher in chronic hypoxic group than in normoxic group in all three subcultures. CONCLUSION: Chronic hypoxia could enhance the mRNA expression of cyclooxygenase-2 caused by acute hypoxia in PASMC of rats. It might be responsible for the lower HPV under chronic hypoxia.

Animals↗
PubMed2001

Effects of extrinsic positive end-expiratory pressure on work of breathing in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the effects of extrinsic positive end-expiratory pressure (PEEPe) on work of breathing in patients with chronic obstructive pulmonary disease (COPD) and their corresponding mechanism. METHODS: Ten ventilated patients with COPD were included in the study. A Bicore CP-100 pulmonary monitor (Bicore Monitoring System, USA) was used for monitoring respiratory mechanics. First, dynamic intrinsic positive end-expiratory pressure (PEEPi, dyn) was measured when PEEPe was zero, which was called PEEPi, dynz. Then the PEEPe was set randomly at 0%, 40%, 60%, 80% and 100% of PEEPi, dynz respectively. Pulmonary mechanics and other parameters (heart rate, blood pressure and blood gas analysis) were measured 30 minutes after the level of PEEPe was changed. RESULTS: Work of breathing patient (WOBp), pressure time product, difference of esophageal pressure and PEEPi, dyn decreased significantly when PEEPe was applied, and continued decreasing as PEEPe was increased. Work of breathing ventilator increased significantly when PEEPe was increased to 80% and 100% of PEEPi, dynz. Significantly positive linear correlation was found between the changes in WOBp and in PEEPi, dyn. CONCLUSIONS: WOBp decreases gradually as PEEPe is increased. WOBp decreases by narrowing the difference between the alveolus pressure and the central airway pressure at the end of expiration when PEEPe is applied.

Aged↗
PubMed2001

Effects of extrinsic positive end-expiratory pressure on cardiopulmonary function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To choose one optimal extrinsic positive end-expiratory pressure (PEEPe) for ventilated patients with chronic obstructive pulmonary disease (COPD) and to compare two methods for choosing the optimal level of PEEPe. METHODS: Ten ventilated patients with COPD were included in the study. First, static intrinsic positive end-expiratory pressure (PEEPi, st) was measured when PEEPe was zero, and the PEEPi, st was called PEEPi, stz. PEEPe at 0%, 40%, 50%, 60%, 70%, 80%, 90% and 100% of PEEPi, stz, respectively, were applied randomly. Respiratory mechanics, hemodynamics, and oxygen dynamics were recorded 30 minutes after the level of PEEPe was changed. RESULTS: When PEEPe was not higher than 80% of PEEPi, stz, no measurement changed significantly. When PEEPe was increased to 90% and 100% of PEEPi, stz, PEEPi, st, peak inspiratory pressure, plateau pressure, pulmonary capillary wedge pressure and central venous pressure increased significantly, P < 0.01. Cardiac output and left ventricular work index decreased significantly, P < 0.01. Oxygen delivery decreased significantly, P < 0.05. When PEEPe was increased to 100% of PEEPi, stz, the right ventricular work index decreased significantly, P < 0.05. CONCLUSION: Eighty percent of PEEPi, stz was the upper limit of PEEPe. The results of the two methods used to set the level of PEEPe were identical.

Aged↗
PubMed2001

[The effects of extrinsic positive end-expiratory pressure on work of breathing in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the effect of extrinsic positive end-expiratory pressure(PEEPe) on work of breathing in chronic obstructive pulmonary disease (COPD) patients and its mechanism. METHODS: 10 ventilated patients [4 males and 6 females with mean age of (70.1 +/- 5.5) years] with exacerbation of COPD were admitted into the study. All the patients' cardiopulmonary functions were stable, and they could receive pressure support ventilation (PSV). Patients with sever heart dysfunction, hepatic dysfunction, renal dysfunction or fever were ruled out. Each patient had an esophagus balloon pressure sensor inserted, and the esophagus balloon was properly positioned using "occlusion test". Flow sensor was placed at the end of tracheal tube opening. Then esophagus balloon pressure sensor and flow sensor were connected with Bicore CP-100 pulmonary monitor. Dynamic intrinsic positive end-expiratory pressure (PEEPi, dyn), difference of esophagus pressure (dPes), work of breathing patient (WOBp), work of breathing ventilator (WOBv), pressure time product (PTP), tidal volume (Vt), respiratory rate (RR), minute ventilation (MV), peak inspiratory flow rate (PIFR), peak expiratory flow rate (PEFR), expiratory airway resistance (Rawe), fraction of inspiration (Ti/Ttot) and so on were measured. PEEPi,dyn was measured by esophagus balloon technique. Electrocardiogram and noninvasive blood pressure modes were added to HP M1165A monitor. Heart rate (HR) and blood pressure (BP) were also measured. Arterial blood was analyzed to measure pH, partial pressure of oxygen in arterial blood (PaO(2)), partial pressure of carbon dioxide in arterial blood (PaCO(2)) and saturation of arterial blood oxygen (SaO(2)). At first, PEEPi, dyn was measured when PEEPe was zero, which was called PEEPi, dynz and was set as baseline. Then PEEPe was set randomly, which was 0%, 40%, 60%, 80% and 100% of PEEPi, dynz respectively. Other parameters remained stable. All the indexes were measured 30 minutes after the level of PEEPe was changed. RESULTS: WOBp decreased as PEEPe increased, from (1.08 +/- 0.49) J/L of PEEPe-0% of PEEPi,dynz to (0.57 +/- 0.32) J/L of PEEPe-100% of PEEPi, dynz, and significant difference was found between each level of PEEPe and the baseline (P < 0.01). But we didn't find significant difference between PEEPe-80% of PEEPi,dynz and PEEPe-100% of PEEPi, dynz. WOBv increased significantly as PEEPe increased, from (1.50 +/- 0.47) J/L of PEEPe-0% of PEEPi, dynz to (1.82 +/- 0.56) J/L of PEEPe-80% of PEEPi, dynz and (1.85 +/- 0.48) J/L of PEEPe-100% of PEEPi,dynz(P < 0.01). The total WOB (WOBp + WOBv) remained steady. PTP trended to decrease, from (153.6 +/- 76.8) cm H(2)O x s x m(-1) of PEEPe-0% of PEEPi, dynz to (86.9 +/- 45.9) cm H(2)O x s x m(-1) of PEEPe-100% of PEEPi, dynz; the difference of PTP between PEEPe-40% of PEEPi,dynz and PEEPe-0% of PEEPi, dynz was significant(P < 0.05), the differences between other levels of PEEPe and PEEPe-0% of PEEPi, dynz were very significant (P < 0.01), but no significant difference was found between PEEPe-80% of PEEPi, dynz and PEEPe-100% of PEEPi, dynz. PEEPi,dyn also decreased significantly as PEEPe increased, from (7.70 +/- 1.42) cm H(2)O of PEEPe-0% of PEEPi, dynz to (2.10 +/- 0.57) cm H(2)O of PEEPe-100% of PEEPi, dynz, very significant differences were found between each level of PEEPe and the baseline (P < 0.01). Significant positive linear correlation was found between DeltaWOBp and DeltaPEEPi, dyn were(r = 0.609, P < 0.01, n = 10). dPes decreased as PEEPe increased, from (15.20 +/- 4.16) cm H(2)O of PEEPe-0% of PEEPi, dynz to (8.20 +/- 4.13) cm H(2)O of PEEPe-100% of PEEPi, dynz, and very significant differences were found between each level of PEEPe and the baseline (P < 0.01). But the difference between PEEPe-80% of PEEPi, dynz and PEEPe-100% of PEEPi, dynz wasn't significant, even dPes of PEEPe-100% of PEEPi, dynz was higher than that of PEEPe-80% of PEEPi, dynz. Vt didn't change markedly. RR, MV and f/Vt increased slightly. Both PIFR and PEFR didn't change markedly. At the same time, HR, BP and blood gas analysis were investigated, but no significant change was found. CONCLUSION: PEEPe can reduce WOBp significantly and improve the coordination between the patient and ventilator. It is shown that decrement of pressure difference between alveolar and central airway leads to decrement of WOBp.

Aged↗
PubMed2001

[Measurement of distortion product otoacoustic emissions in guinea pig].

OBJECTIVE: To establish a stable detecting method of distortion product otoacoustic emissions (DPOAEs). METHOD: After cutting off tragus, seven healthy pigmented guinea pigs (thirteen ears) were selected to measure the DPOAEs at the frequency of 2f1-f2 (cubic DPOAEs). The I/O function and latency at f2 = 2, 4, 6 kHz were analyzed. RESULT: The incidence of DPOAEs at all frequencies was 100%. The maximal amplitude of input-output function was (27.24 +/- 4.15) dB SPL, (27.98 +/- 4.05) dB SPL and (41.45 +/- 1.20) dB SPL respectively; latency was (2.06 +/- 0.21) ms, (1.52 +/- 0.16) ms and (1.37 +/- 0.08) ms at the corresponding frequencies. CONCLUSION: After the improvement of detection, it is satisfactory to measuring DPOAE in animals because of the high incidence, high amplitude and good repetition.

Animals↗
PubMed2001

[Contralateral suppression of latency during distortion product otoacoustic emissions detection in guinea pigs].

OBJECTIVE: To investigate the cochlear micromechanics and the function of cochlear efferent system by detecting the distortion product otoacoustic emissions (DPOAE) with or without contralateral acoustic stimulation. METHODS: The DPOAE amplitude and latency of the cubic DPOAE (2f1-f2) were measured at f2 = 2, 4 and 6 kHz with or without 70 dB SPL broad-band noise contralateral stimulation in ears of 12 healthy pigmented guinea pigs, which were divided into two groups(A and B) and tested with different primary intensity level combinations. On the next day, an operation was made to open the acoustic bulla of right ear in Group A. Kainic Acid (KA, 1 microL of 60 mmol/L) was applied onto the round window membrane and wiped up carefully after three hours. The amplitude and latency of the cubic DPOAE from the left ear were measured after 6 hours of KA administration, with or without contralateral noise stimulation. RESULTS: Before the KA treatment, the amplitude of DPOAE induced by primaries of equal levels (L1 = L2) presented no significant change and the latency prolonged significantly during contralateral acoustic stimulation (Group A). But the amplitude at 2, 4 kHz of DPOAE induced by primaries of different levels (L1 > L2) decreased significantly and the latency also prolonged significantly (Group B). After KA administration in the contralateral ear of Group A, the contralateral acoustic stimulation had no significant effect on either amplitude or latency of DPOAE measured ipsilaterally. CONCLUSION: The result demonstrates that the latency is a sensitive index for the cochlear contralateral suppression. The efferent system may act as a negative feedback during the cochlear transduction.

Acoustic Stimulation↗
PubMed2000

A novel peroxiredoxin of the plant Sedum lineare is a homologue of Escherichia coli bacterioferritin co-migratory protein (Bcp).

We cloned a gene encoding a 17-kDa protein from a cDNA library of the plant Sedum lineare and found that its deduced amino acid sequence showed similarities to those of Escherichia coli bacterioferritin co-migratory protein (Bcp) and its homologues, which comprise a discrete group associated with the peroxiredoxin (Prx) family. Studies of the recombinant 17-kDa protein produced in E. coli cells revealed that it actually had a thioredoxin-dependent peroxidase activity, the hallmark of the Prx family. PrxQ, as we now designate the 17-kDa protein, had two cysteine residues (Cys-44 and Cys-49) well conserved among proteins of the Bcp group. These two cysteines were demonstrated to be essential for the thioredoxin-dependent peroxidase activity by analysis of mutant proteins, suggesting that these residues are involved in the formation of an intramolecular disulphide bond as an intermediate in the reaction cycle. Expression of PrxQ suppressed the hypersensitivity of an E. coli bcp mutant to peroxides, indicating that it might exert an antioxidant activity in vivo.

Amino Acid Sequence↗
PubMed2000

Human lactoferrin binds and removes the hemoglobin receptor protein of the periodontopathogen Porphyromonas gingivalis.

Porphyromonas gingivalis possesses a hemoglobin receptor (HbR) protein on the cell surface as one of the major components of the hemoglobin utilization system in this periodontopathogenic bacterium. HbR is intragenically encoded by the genes of an arginine-specific cysteine proteinase (rgpA), lysine-specific cysteine proteinase (kgp), and a hemagglutinin (hagA). Here, we have demonstrated that human lactoferrin as well as hemoglobin have the abilities to bind purified HbR and the cell surface of P. gingivalis through HbR. The interaction of lactoferrin with HbR led to the release of HbR from the cell surface of P. gingivalis. This lactoferrin-mediated HbR release was inhibited by the cysteine proteinase inhibitors effective to the cysteine proteinases of P. gingivalis. P. gingivalis could not utilize lactoferrin for its growth as an iron source and, in contrast, lactoferrin inhibited the growth of the bacterium in a rich medium containing hemoglobin as the sole iron source. Lactoferricin B, a 25-amino acid-long peptide located at the N-lobe of bovine lactoferrin, caused the same effects on P. gingivalis cells as human lactoferrin, indicating that the effects of lactoferrin might be attributable to the lactoferricin region. These results suggest that lactoferrin has a bacteriostatic action on P. gingivalis by binding HbR, removing it from the cell surface, and consequently disrupting the iron uptake system from hemoglobin.

Anti-Bacterial Agents↗
PubMed2000

Metabolism of the dorsal cochlear nucleus in rat brain slices.

In vitro brain slices of the cochlear nucleus have been used for electrophysiological and pharmacological studies. More information is needed about the extent to which the slice resembles in vivo tissue, since this affects the interpretation of results obtained from slices. In this study, some chemical parameters of the dorsal cochlear nucleus (DCN) in rat brain slices were measured and compared to the in vivo state. The activities of malate dehydrogenase and lactate dehydrogenase were reduced in some DCN layers of incubated slices compared to in vivo brain tissue. The activities of choline acetyltransferase and acetylcholinesterase were increased or unchanged in DCN layers of slices. Adenosine triphosphate (ATP) concentrations for in vivo rat DCN were similar to those of cerebellar cortex. Compared with in vivo values, ATP concentrations were decreased in the DCN of brain slices, especially in the deep layer. Vibratome-cut slices had lower ATP levels than chopper-cut slices. Compared with the in vivo data, there were large losses of aspartate, glutamate, glutamine, gamma-aminobutyrate and taurine from incubated slices. These amino acid changes within the slices correlated with the patterns of release from the slices.

Acetylcholinesterase↗
PubMed2000

PRL-1 PTPase expression is developmentally regulated with tissue-specific patterns in epithelial tissues.

The mechanisms controlling tyrosine phosphorylation of cellular proteins are important in the regulation of many cellular processes, including development and differentiation. Protein tyrosine phosphatases (PTPases) may be as important as protein tyrosine kinases (PTKs) in these processes. PRL-1 is a distinct PTPase originally identified as an immediate-early gene in liver regeneration whose expression is associated with growth in some tissues but with differentiation in others. We now demonstrate that the PRL-1 protein is expressed during development in a number of digestive epithelial tissues. It is expressed at variable time points in the developing intestine, but its expression is limited to the developing villus enterocytes. In the gastric epithelium, PRL-1 expression in the adult is restricted to zymogen cells. PRL-1 is also expressed in the developing liver and esophagus and in the epithelia of the kidney and lung. In each of these contexts, the expression of PRL-1 is associated with terminal differentiation, suggesting that it may play a role in this important developmental process.

Age Factors↗
PubMed2000

Ratiometry of transmembrane voltage-sensitive fluorescent dye emission in hearts.

Transmembrane voltage-sensitive fluorescence measurements are limited by baseline drift that can obscure changes in resting membrane potential and by motion artifacts that can obscure repolarization. Voltage-dependent shift of emission wavelengths may allow reduction of drift and motion artifacts by emission ratiometry. We have tested this for action potentials and potassium-induced changes in resting membrane potential in rabbit hearts stained with di-4-ANEPPS [Pyridinium, 4-(2-(6-(dibutylamino)-2-naphthalenyl) ethenyl)-1-(3-sulfopropyl)-, hydroxide, inner salt] using laser excitation (488 nm) and a two-photomultiplier tube system or spectrofluorometer (resolution of 500-1,000 Hz and <1 mm). Green and red emissions produced upright and inverted action potentials, respectively. Ratios of green emission to red emission followed action potential contours and exhibited larger fractional changes than either emission alone (P < 0.001). The largest changes and signal-to-noise ratio (signal/noise) were obtained with numerator wavelengths of 525-550 nm and denominator wavelengths of 650-700 nm. Ratiometry lessened drift 56-66% (P < 0.015) and indicated decreases in resting membrane potential. Ratiometry lessened motion artifacts and increased magnitudes of deflections representing phase-zero depolarizations relative to total deflections by 123-188% in intact hearts (P < 0.02). Durations of action potentials at different pacing rates, temperatures, and potassium concentrations were independent of whether they were measured ratiometrically or with microelectrodes (P > or = 0.65). The ratiometric calibration slope was 0.017/100 mV and decreased with time. Thus emission ratiometry lessens the effects of motion and drift and indicates resting membrane potential changes and repolarization.

Animals↗
PubMed2000

[The role of mtDNA deletion in the sensitivity to aminoglycoside antibiotic induced deafness].

OBJECTIVE: To establish an animal model of mitochondrial DNA (mtDNA) deletion and investigate the possible role of mtDNA deletion in aminoglycoside antibiotic induced deafness. METHODS: Thirty wistar rats (4 months) were randomly divided into group A and B. Doxorubicin (DOX) was subcutaneously injected at doses of 2 mg/kg twice per week for 3 months in group A and then kanamycin (KM) was intraperitoneally injected 500 mg/kg per day for 10 consecutive days. The treatments of group B were identical to group A, except normal saline was substituted for DOX. The thresholds of auditory brainstem response (ABR) were measured before and after the drug administrations. The inner ear membranous labyrinthine tissue was harvested and mtDNA was amplified to identify 4,834 bp deletion by PCR technique. RESULTS: The elevation of the mean ABR thresholds in group A(67.08 +/- 8.59) dB peSPL was significantly higher than that in group B (12.71 +/- 4.42) dB peSPL after KM administration (P < 0.001). In group A, 9 of the 15 rats demonstrated 4,834 bp mtDNA deletion. However, mtDNA 4,834 bp deletion was negative in group B animals. CONCLUSION: DOX can induce mtDNA deletion in the inner ear tissue of the rat. mtDNA deletion in the inner ear may play an important role in the hypersensitivity to aminoglycoside antibiotic ototoxicity.

Animals↗
PubMed1999

Basolateral proteinase-activated receptor (PAR-2) induces chloride secretion in M-1 mouse renal cortical collecting duct cells.

1. Using RT-PCR, Northern blot analysis, and immunocytochemistry, we confirmed renal expression of proteinase-activated receptor (PAR-2) and demonstrated its presence in native renal epithelial and in cultured M-1 mouse cortical collecting duct (CCD) cells. 2. We investigated the effects of a PAR-2 activating peptide (AP), corresponding to the tethered ligand that is exposed upon trypsin cleavage, and of trypsin on M-1 cells using patch-clamp, intracellular calcium (fura-2) and transepithelial short-circuit current (ISC) measurements. 3. In single M-1 cells, addition of AP elicited a concentration-dependent transient increase in the whole-cell conductance. Removal of extracellular Na+ had no effect while removal of Cl- prevented the stimulation of outward currents. The intracellular calcium concentration increased significantly upon application of AP while a Ca2+-free pipette solution completely abolished the electrical response to AP. 4. In confluent monolayers of M-1 cells, apical application of AP had no effect on ISC whereas subsequent basolateral application elicited a transient increase in ISC. This increase was not due to a stimulation of electrogenic Na+ absorption since the response was preserved in the presence of amiloride. 5. The ISC response to AP was reduced in the presence of the Cl- channel blocker diphenylamine-2-carboxylic acid on the apical side and abolished in the absence of extracellular Cl-. 6. Trypsin elicited similar responses to those to AP while application of a peptide (RP) with the reverse amino acid sequence of AP had no effect on whole-cell currents or ISC. 7. In conclusion, our data suggest that AP or trypsin stimulates Cl- secretion by Ca2+-activated Cl- channels in M-1 CCD cells by activating basolateral PAR-2.

Amino Acid Sequence↗