Biomedical subjects

M Srinivas

Publications and source records attributed to M Srinivas.

At least 73 records · Page 4Linked to original sources

PubMed1999

T-lymphocyte subsets in the contralateral testis after unilateral blunt testicular trauma in pre-pubertal mice.

Although spermatozoa express antigens, they normally do not produce an immunological response because of the blood-testis barrier and the predominance of CD8(+) T-lymphocytes in the rete testis. Unilateral blunt testicular trauma (UBTT) has been reported to decrease fertility. The present study was designed to evaluate the sub-populations of T-lymphocytes in mice with testicular trauma. Twenty male mice aged 20 days were randomized into control and test groups. At about 70 days of age the contralateral testis was harvested, cell suspensions were prepared, and immunofluorescence staining was performed for detection of CD4(+ )and CD8(+) T-lymphocytes by flow-cytometry. The ratio of CD8(+) and CD4(+) lymphocytes was significantly higher (P < 0.001) in the control mice compared to the UBTT group (1.3 +/- 0.3 vs 0.5 +/- 0.01). The results suggest that UBTT alters the CD8(+)/CD4(+) ratio in the contralateral testis, which may have an important bearing on the pathogenesis of infertility in cases of testicular injury.

Animals↗

PubMed1999

Unilateral blunt testicular trauma in pre-pubertal rats.

Injury to the testis breaching the tunica albuginea is known to affect fertility. Blunt testicular trauma with an intact tunica albuginea has been reported to have no effect on contralateral testicular histology and Johnsen testicular maturation score. However, sensitive techniques like DNA flowcytometry have not been utilized so far to evaluate contralateral testicular germ-cell changes. Sixty-four male Wistar rats aged 20 days were randomized into groups I (control), II (unilateral blunt testicular trauma, UBTT), III (UBTT and excision of ipsilateral testis at 6 h), and IV (UBTT and cyclosporine for 30 days). Fertility, DNA flow cytometry of contralateral testicular tissue, and anti-sperm antibodies (ASA) were evaluated. Fertility and haploid-cell percentage of the contralateral testis were significantly decreased compared to controls in early adulthood (100 days). Around 150 days of age, as ASA decreased significantly, fertility and contralateral testicular haploid-cell population recovered and were comparable to the controls. Excision of the traumatized testicle around 6 h after injury or administration of cyclosporine for 30 days protected fertility and the contralateral testis. In contrast to group II rats, ELISA for ASA was negative in group III and IV rats. UBTT affects the contralateral testis and fertility. ASA mediate this damage. Orchidectomy performed around 6 h after trauma or short-term cyclosporine therapy prevents the damage.

Animals↗

PubMed1999

Experimental unilateral undescended testis: gubernaculectomy and anchoring or direct suture fixation?

This study was designed to evaluate whether creation of a unilateral undescended testis (U/L UDT) in rats by direct fixation of the testis can lead to changes in the contralateral (C/L) descended testis, and if so, whether this inherent problem of the model could be eliminated by anchoring the divided gubernaculum to indirectly fix the testis. Thirty male newborn rats were divided into three groups of 10 each and the procedure done on the 2nd day of life to create U/L UDT according to the group allocated: group I: sham-operated; group II: anchoring the gubernaculum after gubernaculectomy; group III: Direct suture fixation of the testis. Fertility, C/L testicular weight (TW), Johnsen score, seminiferous tubular diameter (STD), DNA flow cytometry, and serum anti-sperm antibodies (ASA) were studied. Fertility, C/L TW, Johnsen score, STD, and haploid cell population were significantly reduced in group III compared to group II, while significantly higher titers of ASA were found in group III. Gubernaculectomy and anchoring the gubernaculum to the anterior abdominal wall is a better technique of creation of experimental UDT, as direct fixation of the testis is potentially detrimental to the C/L normal, descended testis.

Animals↗

PubMed1999

Population-based assessment of the outcome of cataract surgery in an urban population in southern India.

PURPOSE: To assess the outcome of cataract surgery in an urban population in southern India. METHODS: As part of a population-based cross-sectional epidemiologic study, the Andhra Pradesh Eye Disease Study, 2,522 people of all ages, including 1,399 individuals 30 years of age or older, from 24 clusters representative of the population of Hyderabad in southern India underwent a detailed interview and ocular evaluation including logarithm of minimal angle of resolution (logMAR) visual acuity, refraction, slit-lamp biomicroscopy, applanation tonometry, gonioscopy, dilation, cataract grading, aphakia/pseudophakia status, and stereoscopic fundus evaluation. Automated threshold visual fields and slit-lamp and fundus photography were performed when indicated by standardized criteria. Very poor outcome in an eye that had undergone cataract surgery was defined as presenting distance visual acuity worse than 20/200, and poor outcome was defined as visual acuity worse than 20/60 to 20/200. RESULTS: In subjects 50 years of age or older, after adjustment for age and sex distribution, the rate of having had cataract surgery in one or both eyes was 14.6% (95% confidence interval [CI], 11.4% to 17.8%). Of 131 eyes (91 subjects) that had undergone cataract surgery, 28 (21.4%; 95% CI, 14.4% to 28.4%) had very poor outcome and another 40 (30.5%; 95% CI, 22.6% to 38.4%) had poor outcome. The very poor outcome in 20 (71.4%) of 28 eyes and poor outcome in 23 (57.5%) of 40 eyes could be attributed to surgery-related causes or inadequate refractive correction. With multivariate analysis, very poor outcome as a result of surgery-related causes or inadequate refractive correction was more likely to be associated with intracapsular cataract extraction than with extracapsular cataract extraction (odds ratio, 9.34; 95% CI, 2.49 to 35.06) in subjects belonging to the lowest socioeconomic status (odds ratio, 4.92; 95% CI, 1.16 to 20.93) and with date of surgery 3 or fewer years before the survey than with more than 3 years (odds ratio, 4.52; 95% CI, 1.33 to 15.39). Also, very poor or poor outcome as a result of surgery-related causes or inadequate refractive correction was associated with women (odds ratio, 2.55; 95% CI, 1.06 to 6.16). CONCLUSIONS: The very high rate of very poor and poor visual outcome, predominantly as a result of surgery-related causes and inadequate refractive correction, in this urban population of India suggests that more attention is needed to improve the visual outcome of cataract surgery. In order to deal with cataract-related visual impairment in India, as much emphasis on surgical quality, refractive correction, and follow-up care is necessary as on the number of surgeries.

Adult↗

PubMed1999

Burden of moderate visual impairment in an urban population in southern India.

OBJECTIVE: To assess the prevalence and causes of moderate visual impairment in an urban population in southern India. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 2522 (85.4% of the eligible) persons of all ages, including 1399 persons 30 years of age or older, from 24 clusters representative of the population of Hyderabad city. TESTING: The eligible subjects underwent a detailed ocular evaluation, including logarithm of the minimum angle of resolution (logMAR) visual acuity, refraction, slit-lamp biomicroscopy, applanation tonometry, gonioscopy, cataract grading, and stereoscopic dilated fundus evaluation. Automated threshold visual fields and slit-lamp and fundus photography were done when indicated by standardized criteria. MAIN OUTCOME MEASURE: Moderate visual impairment was defined as presenting distance visual acuity less than 20/40 to 20/200 or visual field loss by predefined standardized conservative criteria in the better eye. RESULTS: In addition to the 1% prevalence of blindness in this sample reported earlier, moderate visual impairment was present in 303 subjects, an age-gender-adjusted prevalence of 7.2% (95% confidence interval [CI], 4.5%-9.9%; design effect, 2.7). The major cause of moderate visual impairment was refractive error (59.4%, 95% CI, 52.3%-66.5%) followed by cataract (25.3%, 95% CI, 19%-31.6%). Multivariate analysis showed that the prevalence of moderate visual impairment was significantly higher in those 40 years of age or older (odds ratio, 10.9; 95% CI, 8-15) and females (odds ratio, 1.89; 95% CI, 1.41-2.53) and lower in those belonging to the highest socioeconomic status (odds ratio, 0.27; 95% CI, 0.14-0.51). However, because of the pyramidal age distribution of the population, 38.1% of the total moderate visual impairment was present in those younger than 40 years of age. The proportion of moderate visual impairment caused by refractive error was higher in the younger than in the older age groups (P < 0.0001). CONCLUSIONS: Projecting the results to the 26.5% urban population of India, there would be 18.4 million (95% CI, 11.5-25.2 million) persons with moderate visual impairment in urban India alone. Refractive error was the major cause of moderate visual impairment in the population studied. The absolute proportion of moderate visual impairment in those younger than 40 years of age was considerable. The eyecare policy of India, apart from dealing with blindness, should address the issue of the relatively easily treatable uncorrected refractive error as the cause of moderate visual impairment in an estimated 10.9 million persons in urban India.

Adolescent↗

PubMed1999

TPA induced expression and function of human connexin 26 by post-translational mechanisms in stably transfected neuroblastoma cells.

Connexin 26 (Cx26) has been proposed to be a tumor suppressor gene and its expression may modulate development, cell growth and differentiation in various tissues, including the brain. 12-O-tetradecanoylphorbol-13-acetate (TPA) may serve as either tumor promoter (in mammary gland amd skin) or as a differentiating agent (in neuroblastoma and leukemic cells) and may also modulate expression, function and phosphorylation of gap junctions. In this study, to determine the effects of TPA on Cx26 expression and its function in neuroblastoma, we transfected N2A mouse neuroblastoma cells (which are gap junction deficient) with the coding region of human Cx26 gene (which lacks TPA response elements) and examined the changes of expression and function of Cx26 following 10 nM TPA treatment. Individual clones of transfectants stably expressed distinct levels of exogenous Cx26 as judged by Northern and Western blots, immunocytochemistry and electrophysiological recordings. Cx26 channels displayed unitary conductances of about 140-155 pS. Increase of Cx26 expression following TPA treatment was markedly observed using immunocytochemistry and Western blots of membrane fractions although it was not detected in Northern or Western blots of whole cells. This increase in Cx26 expression in the plasma membrane was accompanied by an increase of function as evidenced in measurements of junctional conductance. These results suggest that induction of exogenous Cx26 in neuroblastoma cells by TPA treatment is controlled by post-translational mechanisms.

Animals↗

PubMed1999

Refractive errors in an urban population in Southern India: the Andhra Pradesh Eye Disease Study.

PURPOSE: To assess the prevalence, distribution, and demographic associations of refractive error in an urban population in southern India. METHODS: Two thousand five hundred twenty-two subjects of all ages, representative of the Hyderabad population, were examined in the population-based Andhra Pradesh Eye Disease Study. Objective and subjective refraction was attempted on subjects >15 years of age with presenting distance and/or near visual acuity worse than 20/20 in either eye. Refraction under cycloplegia was attempted on all subjects < or =15 years of age. Spherical equivalent >0.50 D in the worse eye was considered as refractive error. Data on objective refraction under cycloplegia were analyzed for subjects < or =15 years and on subjective refraction were analyzed for subjects >15 years of age. RESULTS: Data on refractive error were available for 2,321 (92.0%) subjects. In subjects < or =15 years of age, age-gender-adjusted prevalence of myopia was 4.44% (95% confidence interval [CI], 2.14%-6.75%), which was higher in those 10 to 15 years of age (odds ratio, 2.75; 95% CI, 1.25-6.02), of hyperopia 59.37% (95% CI, 44.65%-74.09%), and of astigmatism 6.93% (95% CI, 4.90%-8.97%). In subjects >15 years of age, age-gender-adjusted prevalence of myopia was 19.39% (95% CI, 16.54%-22.24%), of hyperopia 9.83% (95% CI, 6.21%-13.45%), and of astigmatism 12.94% (95% CI, 10.80%-15.07%). With multivariate analysis, myopia was significantly higher in subjects with Lens Opacity Classification System HI nuclear cataract grade > or =3.5 (odds ratio, 9.10; 95% CI, 5.15-16.09), and in subjects with education of class 11 or higher (odds ratio, 1.80; 95% CI, 1.18-2.74); hyperopia was significantly higher in subjects > or =30 years of age compared with those 16 to 29 years of age (odds ratio, 37.26; 95% CI, 11.84-117.19), in females (odds ratio, 1.86; 95% CI, 1.33-2.61), and in subjects belonging to middle and upper socioeconomic strata (odds ratio, 2.10; 95% CI, 1.09-4.03); and astigmatism was significantly higher in subjects > or =40 years of age (odds ratio, 3.00; 95% CI, 2.23- 4.03) and in those with education of college level or higher (odds ratio, 1.73; 95% CI, 1.07-2.81). CONCLUSIONS: These population-based data on distribution and demographic associations of refractive error could enable planning of eye-care services to reduce visual impairment caused by refractive error. If these data are extrapolated to the 255 million urban population of India, among those >15 years of age an estimated 30 million people would have myopia, 15.2 million hyperopia, and 4.1 million astigmatism not concurrent with myopia or hyperopia; in addition, based on refraction under cycloplegia, 4.4 million children would have myopia and 2.5 million astigmatism not concurrent with myopia or hyperopia.

Adolescent↗

PubMed1998

Is current eye-care-policy focus almost exclusively on cataract adequate to deal with blindness in India?

BACKGROUND: India's National Programme for Control of Blindness focuses almost exclusively on cataract, based on a national survey done in the 1980s which reported that cataract caused 80% of the blindness in India. No current population-based data on the causes of blindness in India are available. We assessed the rate and causes of blindness in an urban population in southern India. METHODS: We selected 2954 participants by stratified, random, cluster, systematic sampling from Hyderabad city. Eligible participants were interviewed and given a detailed ocular assessment, including visual acuity, refraction, slitlamp biomicroscopy, applanation intraocular pressure, gonioscopy, dilatation, grading of cataract, stereoscopic fundus assessment, and automated-threshold visual fields. FINDINGS: 2522 participants, including 1399 aged 30 years or more, were assessed. 49 participants (all aged > or =30 years) were blind (presenting distance visual acuity <6/60 or central visual field <200 in the better eye). The rate of blindness among those aged 30 years or more, adjusted for age and sex, was 3.08% ([95% CI 1.95-4.21]). Causes included cataract (29.7%), retinal disease (17.1%), corneal disease (15.4%), refractive error (12.5%), glaucoma (12.1%), and optic atrophy (11.0%). 15.7% of the blindness caused by visual-field constriction would have been missed without visual-field examination. Also without visual-field and detailed dilated-fundus assessments, blindness attributed to cataract would have been overestimated by up to 75.8%. If the use of cataract surgery in this urban population was half that found in this study, which simulates the situation in rural India, cataract would have caused 51.8% (39.4-64.2) of blindness, significantly less than the 80% accepted by current policy. INTERPRETATION: Much of the blindness in this Indian population was due to non-cataract causes. The previous national survey did not include detailed dilated-fundus assessment and visual-field examination which could have led to overestimation of cataract as a cause of blindness in India. Policy-makers in India should encourage well-designed population-based epidemiological studies from which to develop a comprehensive long-term policy on blindness in addition to dealing with cataract.

Adult↗

PubMed1998

Intra-pancreatic splenic artery pseudoaneurysm. A rare complication of chronic calcific pancreatitis.

The authors present the case of a 12-year-old boy with a history of chronic upper abdominal pain. Based on ultrasonography, endoscopic retrograde cholangio-pancreatography, and computerized tomography, a diagnosis of chronic calcific pancreatitis with dilation of the main pancreatic duct and a pseudocyst of the proximal pancreas was made. At surgery, in addition to confirmation of the above findings, a pseudoaneurysm arising from the splenic artery was found in the head and body of the pancreas. Pancreaticoduodenal resection including the pseudoaneurysm was performed. Postoperatively the child developed diabetes, which is easily managed with small doses of insulin.

Aneurysm, False↗

PubMed1998

Effect of cyclosporine on fertility in male rats.

The effect of cyclosporine (CsA) on fertility has assumed greater importance with the increasing numbers of pediatric transplantations being performed all over the world. Conflicting reports on the effects of CsA on sex hormones are available. This experimental animal study was designed to examine the effect of CsA on testicular weight, sperm counts, seminiferous tubular diameter (STD), testicular morphology, DNA flowcytometry, sex hormone levels, and fertility in male rats. Those rats who received CsA (20 mg/kg per day) showed significant reductions in testicular weight (P < 0.05), sperm count (P < 0.01), Johnsen score (P < 0.05), STD (P < 0.01), serum testosterone levels (P < 0.05), haploid cell population (P < 0. 001) in the testis, and fertility (P < 0.001) compared to those receiving CsA 10 mg/kg per day and control rats. These findings will have an important bearing for children receiving cyclosporine for long periods to guide the physician in optimally adjusting long-term treatment.

Animals↗

PubMed1998

Fertility and unilateral undescended testis in the rat model II.

Continuing experimental work on the effect of experimentally created unilateral undescended testis (UL-UDT) in neonatal rats, this study examined the fertility and correlated it to contralateral (CL) testicular morphology, seminiferous tubular diameter (STD), DNA flowcytometry, and the presence of serum anti-sperm antibodies (ASA) at 120-135 days of age. In our previous reported work, the fertility of rats with UL-UDT at 65-80 days of age was the same as that of controls. In the present study the rats with UL-UDT had significantly reduced fertility (P < 0.01) compared to controls, even though the Johnsen scores and mean STD of the CL testicular tissue were comparable. DNA flowcytometry demonstrated a significant decrease (P < 0.001) in haploid cell population in the CL testicular tissue of rats with UL-UDT. Furthermore, the rats with UL-UDT who either received an immunosuppressive or in whom the UDT was excised early showed almost normal fertility and DNA histograms like those of controls. Significantly high titres of serum ASA were detected only in the group with UL-UDT when tested at 135 days of age. From these results, in combination with earlier results on similar work, it may be inferred that UL-UDT causes immunologically-mediated, progressive damage to the CL descended testis, leading to a decrease in fertility in rats.

Aging↗

PubMed1998

Somatic growth and renal function after unilateral nephrectomy for Wilms' tumor.

Solitary kidneys in renal donors and patients who have undergone unilateral nephrectomy for malignant disease have been reported to undergo hyperfiltration injury. This study was undertaken to evaluate the somatic growth and development of followed-up patient after Wilms' tumor to evaluate their renal function and identify any evidence of injury in the remaining kidney. The growth and development of all the children was found to be normal, as was DTPA clearance. Microalbuminuria in 24-h urinary collections was detected in 84% of the patients, indicating evidence of hyperfiltration injury. This study highlights the need for close monitoring of the renal function of long-term follow-up patients after Wilms' tumor in addition to the routine monitoring for tumor recurrence.

Albuminuria↗

PubMed1998

The Internet and the paediatric surgeon.

The Internet, which has truly united the world, is an extensive network of inter-linked computers storing immense bytes of information that can be accessed by anyone, transcending all barriers. The paediatric surgery Internet consists of exponentially growing material that deals with information specifically for paediatric surgeons and patients of the paediatric age group. We reviewed the methods available to take advantage of this network to enable busy paediatric surgeons to accrue the benefits easily and efficiently rather than be lost in the information ocean by surfing individually. By getting connected to the Internet, the paediatric surgeon gains enormous information that can be useful for patient care. The Internet has revolutionised scientific publications by virtue of its fast and accurate transmission of manuscripts. Paediatric surgeons can send manuscripts by this channel and also access journals, obviating the inherent lag period of communication by post.

Communication↗

PubMed1998

The syndromic classification of the International League Against Epilepsy: a hospital-based study from South India.

PURPOSE: To determine the distribution of various epilepsies and epileptic syndromes in the epileptic population treated in a university hospital in a developing country. METHODS: Data concerning 2,531 patients with epilepsy seen between January 1989 and June 1994 were analyzed using the International League Against Epilepsy (ILAE) classification. RESULTS: Of 2,531 cases, 48% fell into ILAE categories 1.3, 3.2, or 4.1 (cryptogenic, without unequivocal generalized or focal seizures; or situation-related seizures, respectively). Localization-related epilepsies (LREs) and epileptic syndromes (1.1, 1.2, 1.3) were found in 1,591 (62.9%) patients; of these patients, symptomatic localization-related epilepsies totaled 62.7%. and idiopathic localization-related epilepsies accounted for only 0.7%. Juvenile myoclonic epilepsy was the most common type of idiopathic generalized epilepsy (IGE), comprising 4.9% of the total study population and 7.7% of patients registered in the epilepsy clinic. A combination of childhood and juvenile absence epilepsies were found in only 0.4% of the total study population. Single computed tomography (CT) enhancing lesion (SCTEL) and focal cerebral calcification (FCC) accounted for 22% of the etiologic factors for localization-related epilepsies. Neurologic deficits were found in 9.5% of patients with SCTEL; none were found with FCC. None of the patients with these lesions had any history of antecedent events that suggested CNS involvement. In patients with localization-related epilepsies with unremarkable clinical data, the proportion of CT scans showing SCTELs was 39 (95% confidence interval [CI], 0.35-0.43) and 0.18 (95% CI, 15-0.21) for FCCs. The proportion for both lesions together was 0.57 (95% CI, 0.53-0.61). Seizures did not recur once the lesion resolved in patients with SCTELs. In patients with FCCs, seizure remission was 71.5% (95% CI, 53.7-85.4) at 3 years. CONCLUSIONS: This study illustrates the rarity in one patient population of some of the syndromes and categories described in the ILAE classification. Childhood and juvenile absence epilepsies together formed a small proportion. SCTEL and FCC were important etiologic factors for localization related epilepsies. The epilepsy associated with SCTEL was a form of benign epilepsy; epilepsy associated with FCC had remission rates similar to other remote symptomatic epilepsies. Without neuroimaging evidence, these 2 lesions would have been missed and the patients might have been grouped under cryptogenic localization related epilepsy. For this reason, we emphasize the need for neuroimaging in patients with localization related epilepsies with unremarkable clinical findings, before classification into the cryptogenic category. In the absence of neuroimaging, such patients should be classified as "probably cryptogenic."

Adolescent↗

PubMed1997

Differential A1 adenosine receptor reserve for two actions of adenosine on guinea pig atrial myocytes.

Adenosine activates adenosine-induced inwardly rectifying K+ current (IKAdo) and inhibits isoproterenol (100 nM)-stimulated L-type Ca2+ current (beta-ICa,L) of guinea pig atrial myocytes with EC50 values of 2.17 and 0.20 microM, respectively. We determined whether this 11-fold difference in potency of adenosine is due to the existence of a greater A1 adenosine receptor reserve for the inhibition of beta-ICa,L than for the activation of IKAdo. Atrial myocytes were pretreated with vehicle (control) or the irreversible A1 adenosine receptor antagonist 8-cyclopentyl-3-[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxa nthine (FSCPX) (10 and 50 nM) for 30 min, and after a 60-min washout period, concentration-response curves were determined for the adenosine-induced activation of IKAdo and inhibition of beta-ICa,L. Pretreatment of atrial myocytes with 10 nM FSCPX reduced the maximal activation of IKAdo by 60% (7.9 +/- 0.2 to 3.2 +/- 0.1 pA/pF). In contrast, a higher concentration of FSCPX (50 nM) was required to reduce the maximal inhibition of beta-ICa,L by 39% (95 +/- 4% to 58. 7 +/- 5.6%) and caused a 15-fold increase in the EC50 value of adenosine. Values of the equilibrium dissociation constant (KA) for adenosine to activate IKAdo and inhibit beta-ICa,L, estimated according to the method of Furchgott, were 2.7 and 5.6 microM, respectively. These values were used to determine the relationship between adenosine receptor occupancy and response. Half-maximal and maximal activations of IKAdo required occupancies of 40% and 98% of A1 adenosine receptors, respectively. In contrast, occupancies of only 4% and 70%, respectively, of A1 adenosine receptors were sufficient to cause half-maximal and maximal inhibitions of beta-ICa, L. Consistent with this result, a partial agonist of the A1 adenosine receptor SHA040 inhibited beta-ICa,L by 60 +/- 3.5% but activated IKAdo by only 18.1 +/- 2.5%. The results indicate that the A1 adenosine receptor is coupled more efficiently to an inhibition of beta-ICa,L than to an activation of IKAdo.

Adenosine↗

PubMed1996

Nonspecific inhibition of adenosine-activated K+ current by glibenclamide in guinea pig atrial myocytes.

The ATP-sensitive K+ (KATP) channel blocker glibenclamide was reported to inhibit the K+ current activated by adenosine. This study investigated whether the inhibition by glibenclamide of the adenosine-induced current is due to a specific blockade of KATP channels in guinea pig atrial myocytes. In the absence of adenosine, the basal background current was an inward rectifier K+ current (IK1). Glibenclamide at concentrations of 10, 30, and 100 microM reduced the basal background K+ current by 15 +/- 6, 43 +/- 10, and 63 +/- 11%, respectively. In the presence of adenosine (10 microM), glibenclamide (30 microM) decreased the adenosine-induced K+ current by 39 +/- 3%. A similar inhibitory effect of glibenclamide on the outward K+ currents activated by either the muscarinic agonist carbachol or the nonhydrolyzable GTP analogue guanosine 5'-[gamma-thio]triphosphate was observed. A low concentration (1 microM) of glibenclamide did not significantly attenuate the current elicited by adenosine, although it completely abolished the outward K+ current activated by pinacidil, a KATP channel opener. Thus we conclude that the inhibition of adenosine-induced K+ current by glibenclamide at high concentrations (> 1 microM) is not due to a specific blockade of KATP channels, but rather, resulted from a blockade of IK1.

Action Potentials↗

PubMed1996

A novel irreversible antagonist of the A1-adenosine receptor.

We determined the effects of 8-cyclopentyl-3-[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxanth ine (FSCPX), a putative irreversible antagonist of the A1-adenosine receptor, on cardiac A1-adenosine receptor-mediated responses and on the specific binding of [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]CPX) to guinea pig cardiac and brain membranes. FSCPX (5 microM) completely reversed the increase in K+ current of guinea pig atrial myocytes caused by 100 microM adenosine (259 +/- 30 to 20 +/- 7 pA) but had no significant effect on K+ currents caused by either 0.5 microM carbachol or 100 microM GTP gamma S. The attenuation of K+ current by FSCPX was both time and concentration dependent and persisted after washout of the antagonist. Pretreatment of atrial myocytes with FSCPX (50 nM) markedly attenuated the activation of K+ current and the inhibition of isoproterenol-stimulated I(Ca,L) caused by adenosine by 90.1% and 84.2%, respectively, but did not alter the responses of atrial myocytes to carbachol. FSCPX (1 microM) irreversibly antagonized the A1-adenosine receptor-mediated increase in atrioventricular nodal conduction time of isolated perfused guinea pig hearts from 10.5 +/- 0.5 to 0.7 +/- 0.6 msec but did not significantly alter the A2-adenosine receptor-mediated decrease in coronary resistance. Preincubation of guinea pig cardiac membranes with 0.1, 1.0, or 3.0 microM FSCPX for 30 min reduced the Bmax of [3H]CPX binding by 41 +/- 10%, 67 +/- 6%, and 80 +/- 1% (mean +/- standard error, three experiments), respectively, with no significant change in the Kd. Similarly, 0.1 and 1.0 microM FSCPX irreversibly reduced the binding of [3H]CPX to guinea pig forebrain membranes by 65 +/- 5% and 83 +/- 2% (four experiments), respectively, but did not reduce the binding of [3H]CGS 21680, an A2a-adenosine receptor agonist, to striatal membranes. FSCPX did not affect the potency of 5'-guanylylimidodiphosphate to inhibit the binding of [3H]CCPA, an A1-adenosine receptor agonist, to brain membranes. The results indicate that FSCPX is a specific, irreversible, A1-adenosine subtype-selective receptor antagonist.

Adenosine↗

PubMed1995

Ionic basis of the electrophysiological actions of adenosine on cardiomyocytes.

The purpose of this review is to examine the role of the extracellular A1-adenosine (Ado) receptor in modulating membrane potential and currents in cardiac cells. The cellular electrophysiological effects of adenosine are both cell type- and species-dependent. In supraventricular tissues (SA, AV node, and atrium) of all species studied, the "direct" cAMP-independent activation of the inwardly rectifying K+ current IKAdo seems to be the most important action of adenosine. This current is activated by both adenosine and acetylcholine and flows through K+ channels with unitary slope conductance of about 45 pS and an open time constant of 1.4 ms. The density of K(+)-ACh,Ado channels is much less in ventricular than in atrial myocytes, and thus adenosine has little or no effect on the ventricular action potential. In atrial myocytes adenosine has a small inhibitory effect on basal L-type calcium current (ICa,L), but no effect on T-type calcium current (ICa,T). In ventricular myocytes, adenosine does not inhibit ICa,L (except ferret), ICa,T, or the sodium inward current INa. Adenosine has recently been shown to activate IKATP in ventricular membrane patches, but the relevance of this finding remains to be defined. Irrespective of cell type and species, adenosine inhibits membrane currents that are stimulated by beta-adrenergic agonists and other agents known to stimulate the activity of the enzyme adenylyl cyclase. This indirect cAMP-dependent mechanism of action has been shown to be responsible for the inhibition by adenosine of isoproterenol-stimulated ICa,L, delayed rectifier K+ current (IK), chloride current (ICl), the transient inward current ITi, and the pacemaker current IF. The importance of the actions of adenosine on membrane currents in modulation of atrial, ventricular, sinoatrial, and atrioventricular nodal function are discussed. Likewise, the antiarrhythmic and proarrhythmic actions of adenosine are discussed and the clinical implications of these actions are noted.

Adenosine↗