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B Stein

Publications and source records attributed to B Stein.

At least 73 records · Page 4Linked to original sources
PubMed1996

Expression of inducible nitric oxide synthase in failing and non-failing human heart.

Recently, a significant activity of inducible nitric oxide synthase (iNOS) has been reported in biopsies from failing hearts due to idiopathic dilated cardiomyopathy (IDC). Thus, a potential pathophysiological role of iNOS in IDC has been stated. In order to investigate, whether iNOS expression is of pathophysiological relevance in human heart failure, we measured iNOS protein expression and cGMP content in left ventricular myocardium from non-failing and failing human hearts. Immunoblot analysis revealed iNOS protein expression in four out of six failing hearts from septic patients, whereas no iNOS-protein expression was detected in either non-failing human hearts (n = 6) or failing hearts due to IDC (n = 9), ischemic heart disease (IHD, n = 7), Becker muscular dystrophy (BMD, n = 2) and mitoxantrone-induced toxic cardiomyopathy TCM, n = 1). cGMP content was increased by 130% in septic hearts, whereas there was no cGMP increase in hearts with IDC. IHD and BMD compared to non-failing hearts. We conclude, that the induction of iNOS may play a role in contractile dysfunction observed in septic shock, but is unlikely to be of major pathophysiological importance in end-stage heart failure due to IDC, IHD, BMD and TCM.

Animals↗
PubMed1996

Endotoxin and cytokines induce direct cardiodepressive effects in mammalian cardiomyocytes via induction of nitric oxide synthase.

In patients with septic shock or inflammatory cardiac diseases like myocarditis myocardial contractility is depressed. These patients have elevated circulating levels of bacterial endotoxins (lipopolysaccharides, LPS) and pro-inflammatory cytokines like interleukin-1 beta (IL-alpha 1 beta) or tumor necrosis factor-alpha (TNF-alpha). It is not clear, whether LPS and/or cytokines have direct inotropic effects on cardiomyocytes and whether these effects are mediated via the L-arginine-nitric oxide synthase (NOS) pathway as demonstrated in vascular smooth muscle cells. Therefore, we examined the direct effects of LPS. IL-1 beta and TNF-alpha on contractility and cGMP content in isolated guinea-pig ventricular cardiomyocytes. Furthermore, the influence of the NOS inhibitor NG-nitro-L-arginine (L-NNA) and dexamethasone on these effects was studied as well as inducible NOS (iNOS) protein expression. LPS (1000 ng/ml), IL-1 beta (25 ng/ml) and TNF-alpha (100 ng/ml) decreased contractility by 48%, 55% and 65% and augmented cGMP content by 135%, 88% or 70% after long-term treatment (18 h) in cardiomyocytes, without altering contractility or cGMP content after short-term treatment (30 min). These effects were blocked by L-NNA (100 microM) and dexamethasone (3 microM). Furthermore iNOS protein was expressed in LPS- and cytokine-treated cardiomyocytes. These findings demonstrate that LPS. IL-1 beta and TNF-alpha have direct negative inotropic effects on cardiomyocytes, which are accompanied by an increase in cGMP content. These effects are mediated via de novo synthesis of a myocardial iNOS. The direct negative inotropic effects of endotoxins and cytokines on cardiomyocytes may in part contribute to the contractile dysfunction observed in patients with septic shock or inflammatory cardiac diseases.

Animals↗
PubMed1996

Characterization of a stimulatory adenosine A2a receptor in adult rat ventricular myocyte.

The expression and function of stimulatory adenosine A2 receptor on the cardiac myocyte is not well defined. The objective of the present study is to characterize the A2a receptor in adult rat cardiac ventricular myocytes. After selection of an optimal lot of collagenase for myocyte isolation and for consistent measurement of adenosine-mediated responses, the A1-receptor pathway was inactivated by pertussis toxin and by the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine. Effects of the adenosine agonist and antagonist or cardiac myocyte contractile amplitude and on adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined. The A2a-receptor-selective agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoade nos ine (CGS-21680) caused a pronounced stimulation of myocyte contractile amplitude and an increase in the cAMP level, as did the nonselective agonists 5'-(N-ethylcarboxamido) adenosine (NECA) and adenosine. The A2a-receptor-selective antagonist 8-(3-chlorostyryl)caffeine blocked the NECA- and adenosine-induced positive inotropic response. Probing of myocyte RNA with a rat A2a-receptor cDNA demonstrated a 2.6-kb mRNA, corresponding to that encoding the A2a receptor. Together, data from contractile, cAMP, and RNA studies indicate that A2a receptors are expressed and are functionally coupled to stimulation of cAMP accumulation and cardiac contractility in adult rat ventricular myocytes.

Adenosine↗
PubMed1996

Relation between contractile function and regulatory cardiac proteins in hypertrophied hearts.

The aim of this study was to examine the mechanism(s) underlying the reduced isoproterenol-induced positive inotropic and lusitropic effects in hypertrophied hearts. Chronic beta-adrenergic stimulation (2.4 mg isoproterenol.kg-1. day-1 for 4 days) induced cardiac hypertrophy by 33 +/- 2% in rats. A parallel downregulation of phospholamban (PLB) and sarcoplasmic reticulum Ca2(+)-ATPase (SERCA2) protein expression by 49 and 40%, respectively, was observed, whereas troponin I (TNI) and C protein remained unchanged. In papillary muscles from chronically beta-adrenergically stimulated rats, the isoproterenol-induced positive inotropic and lusitropic effects, as well as adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, were attenuated compared with those in control animals. Acute exposure to isoproterenol induced phosphate incorporation into PLB, TNI, and C protein of 48 +/- 4.6, 55 +/- 5.0, and 27 +/- 4.9 pmol/mg homogenate protein, respectively, in control animals. In the hypertrophied hearts, phosphate incorporation into PLB was reduced by 76%, whereas phosphate incorporation into TNI or C protein remained unchanged. In conclusion, chronic beta-adrenergic stimulation reduced the isoproterenol-stimulated positive inotropic and lusitropic effects in papillary muscles, which were accompanied by 1) diminished cAMP formation, 2) attenuation of cAMP-mediated PLB phosphorylation, and 3) downregulation of PLB and SERCA2 protein.

Adenosine Triphosphatases↗
PubMed1996

Positive inotropic effects of the calcium sensitizer CGP 48506 in failing human myocardium.

In trabeculae carneae from failing human myocardium, CGP 48506 increased the force of contraction, which reached 310 +/- 41% of predrug values at 100 mumol/l. Its stereoisomer CGP 48508 did not affect the force of contraction (100 mumol/l). The positive inotropic effect of CGP 48506 was not sensitive to 10 mumol/l carbachol. The positive inotropic effect of CGP 48506 was accompanied by increases in time to peak tension and time of relaxation amounting to 175 +/- 4% and 205 +/- 15% of control, respectively, at 100 mumol/l. CGP 48506 but not CGP 48508 sensitized skinned trabeculae from failing human myocardium to calcium with an EC50 value of 10 mumol/l. However, CGP 48506 and CGP 48508 (up to 300 mumol/l) did not affect the activity of PDE isoenzymes I to IV from failing human myocardium. CGP 48506 is the first inotropic agent with calcium-sensitizing properties in the human heart that has been found to be devoid of inhibitory activity on human cardiac PDE isoenzymes.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty.

BACKGROUND: Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized. METHODS AND RESULTS: Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics. CONCLUSIONS: Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined.

Angina Pectoris↗
PubMed1995

Auriculocephalic index: a new anthropometric index for syndrome delineation.

We describe a new anthropometric index, the "auriculocephalic index." It results from the ratio between the length of auricle and the corresponding preauricular head height. The index is independent of sex and of age. Normally it ranges between 0.25 (-2s) and 0.33 (+2s). In syndrome delineation it may help to diagnose more precisely large or small auricles as phenogenetic variants.

Adolescent↗
PubMed1995

The ryanodine binding sarcoplasmic reticulum calcium release channel in nonfailing and in failing human myocardium.

The ryanodine-sensitive Ca2+ release channel (RyaCRC) of the sarcoplasmic reticulum plays a key role in the intracellular Ca2+ handling in cardiomyocytes. Altered expression of the RyaCRC has been supposed to contribute to abnormal cellular Ca2+ handling and to myocardial dysfunction in dilated and ischemic cardiomyopathy. In the present study the 3H-ryanodine binding site in human myocardial homogenates was characterized and the density of the RyaCRC (which corresponds to the cardiac ryanodine receptor) was determined in nonfailing and in failing human myocardium. Homogenates were prepared from nonfailing left ventricular myocardium from the hearts of 5 organ donors (NF) and from failing myocardium from 14 explanted hearts of transplant recipients with end-stage heart failure resulting from dilated (DCM, n = 5) or ischemic (ICM, n = 9) cardiomyopathy. Radioligand saturation binding experiments revealed a specific, high-affinity 3H-ryanodine binding site (Kd-values: NF: 0.65 +/- 0.11 nmol/l, DCM: 0.66 +/- 0.09 nmol/l, ICM: 0.88 +/- 0.18 nmol/l; n.s.) in all preparations. Specific 3H-ryanodine binding depended on the free Ca2+ concentration in the assay. It was maximal at 3-100 micro mol/l Ca2+. The binding was inhibited by the RyaCRC antagonists ruthenium red (Ki-value: 0.32 [0.18-0.56] micromol/l, n = 5) and Mg2+ (Ki-value: 2.95 [1.23-7.11] mmol/l, n = 5). The RyaCRC density was 103.5 +/- 11.9 fmol/mg protein in nonfailing myocardium. There was no significant change in the RyaCRC density in dilated or ischemic cardiomyopathy (112.4 +/- 17.1 and 122.7 +/- 13.9 fmol/mg protein) compared to nonfailing control myocardium. In summary, 3H-ryanodine binds specifically and with high-affinity to the RyaCRC in human myocardium. There is no change in the RyaCRC density in failing myocardium of patients with DCM or ICM in comparison to non-failing controls.

Adult↗
PubMed1995

A prospective randomized comparison of transurethral resection to visual laser ablation of the prostate for the treatment of benign prostatic hyperplasia.

OBJECTIVES: Transurethral resection of the prostate (TURP) represents the accepted standard of surgical therapy for the management of symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH). However, this is a major operative procedure associated with significant perioperative morbidity. Visual laser ablation of the prostate (VLAP) utilizing a neodymium:yttrium-aluminum-garnet laser represents a new technologic approach to the surgical management of BPH. We compared the relative safety and efficacy of these two surgical approaches in a prospective, randomized trial. METHODS: At 6 investigational sites in the United States, 115 men with symptomatic BPH more than 50 years of age and not in retention, were randomly assigned to undergo either TURP (59 patients) of VLAP (56 patients). VLAP patients received a mean of 10,200 J of energy delivered in a mean of 5.5 intraprostate laser applications. At preoperative baseline, 3 months, 6 months, and 1 year postoperatively, all patients underwent clinical evaluations, including ultrasonic prostatic volume determination, standardized American Urological Association (AUA)-6 symptom score, peak urine flow, postvoid residual urine volume, and quality-of-life assessment. RESULTS: Compared to TURP, the VLAP procedure required less time (23.4 versus 45.2 minutes; P < 0.01) and shorter hospitalization (1.8 versus 3.1 days, P < 0.01). VLAP was associated with a significantly lower rate of serious treatment-related complications compared to TURP (10.7% versus 35.6%; P < 0.01). Only One (2.2%) patient undergoing VLAP experienced a greater than 2.2 g/dL decrease in hemoglobin compared to 40% of TURP patients (P = 0.01). No patient in the VLAP group required blood transfusion compared with 3.4% of those undergoing TURP. Of the 115 patients, clinical outcomes measured at 1 year showed a mean improvement in AUA-6 symptom scores of -9.0 for VLAP compared with -13.3 for TURP (P < 0.04), mean increase in peak urinary flow rate of 5.3 cc/s for VLAP compared with 7.0 cc/s for TURP (P = 0.27), and mean decrease in postvoid residual urine volume of -55.4 cc for VLAP compared with -138.8 cc for TURP (P < 0.01). At 1 year, 78.2% of patients undergoing VLAP indicated that their quality of life was improved compared with 93.0% of patients undergoing TURP (P = 0.03). When compared with TURP, treatment of BPH with VLAP is associated with less hemoglobin decrease, a lower likelihood of serious complication, and requires less procedure time and a shorter hospital stay. Through a 1-year follow-up, VLAP produced significant improvement over baseline in objective and subjective outcome measures. However, for 1-year improvement in AUA-6 symptom score, postvoid residual urine volume, and quality of life, VLAP was less effective than TURP. CONCLUSIONS: In this initial study in the United States, with relatively low-energy laser applications, VLAP did not result in as complete a removal of prostatic tissue as did TURP. Considering the lower morbidity, shorter procedure and hospitalization times, and the degree of effectiveness that was achieved even at the low-energy doses used in this study, VLAP appears to be a viable and safe alternative to standard TURP.

Aged↗
PubMed1995

Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta.

Bone metabolism is regulated by a balance between bone resorption caused by osteoclasts and bone formation caused by osteoblasts. This balance is disturbed in postmenopausal women as a result of lower serum estrogen levels. Estrogen, which is used in hormone replacement therapy to prevent postmenopausal osteoporosis, downregulates expression of the interleukin 6 (IL-6) gene in osteoblasts and bone marrow stromal cells. IL-6 is directly involved in bone resorption by activating immature osteoclasts. We show here that NF-kappa B and C/EBP beta are important regulators of IL-6 gene expression in human osteoblasts. Importantly, the IL-6 promoter is inhibited by estrogen in the absence of a functional estrogen receptor (ER) binding site. This inhibition is mediated by the transcription factors NF-kappa B and C/EBP beta. Evidence is presented for a direct interaction between these two factors and ER. We characterized the protein sequence requirements for this association in vitro and in vivo. The physical and functional interaction depends in part on the DNA binding domain and region D of ER and on the Rel homology domain of NF-kappa B and the bZIP region of C/EBP beta. The cross-coupling between ER, NF-kappa B, and C/EBP beta also results in reduced activity of promoters with ER binding sites. We further show that the mechanism of IL-6 gene repression by estrogen is clearly different from that of activation of promoters with ER binding sites. Therefore, drugs that separate the transactivation and transrepression functions of ER will be very helpful for treatment of osteoporosis without causing undesirable side effects.

Base Sequence↗
PubMed1995

Fetal liver calcifications: sonographic appearance and postnatal outcome.

PURPOSE: To determine the importance of intrahepatic calcifications seen sonographically in the fetus. MATERIALS AND METHODS: The authors retrospectively reviewed sonograms obtained in fetuses scanned between 16 and 40 gestational weeks in whom intrahepatic calcifications were seen. The number and character of these calcifications were determined. Follow-up scans obtained in utero and after birth were also reviewed. Outcome was determined after birth. RESULTS: Thirty-three fetuses had intrahepatic calcifications at 16-38 weeks gestation. Four of the 33 fetuses died, one of which had liver calcifications as the only sonographic finding. This fetus had cytomegalovirus and was the only fetus with increasing numbers of calcifications on follow-up scans. All fetuses with isolated liver calcifications had a normal postnatal outcome (96% survival rate for fetuses with isolated intrahepatic calcifications). Of eight fetuses with additional anomalies, five lived; only two were healthy newborns. CONCLUSION: The outcome in fetuses with isolated intrahepatic calcifications is usually excellent, although viral causes must be excluded if additional findings appear.

Abnormalities, Multiple↗
PubMed1995

Central cholinergic and alpha-adrenergic mediation of gastric slow wave dysrhythmias evoked during motion sickness.

Motion sickness is associated with gastric slow wave disruption. Animal models of slow wave disturbances show dependence on neural and prostaglandin pathways. Roles of these pathways in circular vection-evoked gastric dysrhythmias and nausea were tested. Eight volunteers with histories of motion sickness underwent vection (60 degrees/s), during which nausea (0 = none to 3 = severe) and electrogastrographic parameters were assessed. Tachygastric activity was expressed as the signal percentage at frequencies of > 4.5 cycles/min. Circular vection induced a maximal nausea score of 2.8 +/- 0 at 513 +/- 66 s. Tachygastric activity increased from 18 +/- 2 to 37 +/- 4% (P < 0.05) and peaked before maximal nausea. Atropine reduced nausea scores to 0 +/- 0 (P < 0.01) with no increase in tachygastric activity (14 +/- 6%). In contrast, the peripheral muscarinic antagonist methscopolamine did not reduce tachygastric activity (46 +/- 4%), nausea (1.8 +/- 0.5), or time to maximal tachygastric activity (504 +/- 80 s) with vection. Phentolamine reduced nausea (1.5 +/- 0.3, P < 0.01) and tachygastric activity, and delayed their onset, whereas propranolol and naloxone had no effect. Pretreatment with oral indomethacin (50 mg) three times daily for 3 days had no effect on vection-evoked tachygastric activity or nausea. To conclude, circular vection evokes gastric dysrhythmias that correlate temporally with maximal nausea and are suppressed by atropine, but not methscopolamine, and are reduced by phentolamine. In contrast to other models of slow wave disruption, endogenous prostaglandins play no role. Thus central cholinergic pathways mediate vection-evoked dysrhythmias with additional modulation by alpha-adrenergic pathways.

Adult↗
PubMed1994

The crumpled coronary: an enigma of arteriographic pseudopathology and its potential for misinterpretation.

A series of angioplasty cases is presented in which dynamic alterations in coronary artery configuration developed. These changes were suggestive of extensive, complex dissections. Several common features emerged in these cases of which interventional cardiologists should be aware. These features included complex vessel morphology (tortuous segments, anomalous takeoffs, and complex stenoses) and the use of certain types of PTCA hardware (Amplatz guiding catheters and 0.018-inch wires). This phenomenon, termed pseudo narrowing, remains largely unrecognized. Identification of these characteristics and employment of proper management strategies will ensure a good outcome in these situations when they arise.

Aged↗
PubMed1994

Influence of age on cyclosporin A-induced alterations in bone mineral metabolism in the rat in vivo.

Cyclosporin A (CsA) administered to actively growing young rats produces a high-turnover osteopenia. We investigated and compared the effect of CsA on the bone mineral metabolism in young rats with that of older rats, which have a lower rate of bone turnover. A group of 24 young (9 weeks) and 24 older (9 months) male Sprague-Dawley rats were orally administered 15 mg/kg of CsA or placebo daily for 24 days. Rats were weighed and serum assayed serially for bone gla protein (BGP), parathyroid hormone, ionized calcium, blood urea nitrogen, creatinine, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. After sacrifice, histomorphometric analysis was performed on undecalcified proximal tibial metaphysis with double-fluorescent labeling. Serum BGP levels were significantly elevated in both young and older rats administered CsA, and 1,25-(OH)2D levels were significantly elevated in CsA-treated young rats more than in older rats. Body weight was significantly reduced in CsA-treated older rats. There were mild but significant alterations in renal function in both groups receiving CsA. In the most comprehensive examination to date of the effects of CsA on bone histomorphometry, both young (-44%) and older rats (-20%) lost significant amounts of trabecular bone compared to their respective controls. Bone loss in young rats was mainly due to a reduced number of trabecular; older rats lost mainly trabecular thickness. Microanatomic nodal studies were consistent with these results. These data demonstrate that although cancellous bone loss induced by CsA is more marked in young rats, older rats with slower bone turnover are also at risk.

Administration, Oral↗
PubMed1994

Effect of cyclosporin A on bone mineral metabolism in experimental diabetes mellitus in the rat.

Cyclosporin A (CsA) is widely used in diabetic transplant patients and early type I diabetes mellitus. Diabetes produces a low-turnover osteopenia, and CsA conversely induces high-turnover osteopenia in rats. We investigated whether CsA would exacerbate diabetic osteopenia. Four groups of 10-week-old male Sprague-Dawley rats (n = 11/group) were studied: On day -6, groups A and C received saline and groups B and D received intravenous streptozotocin (55 mg/kg) to induce diabetes. From day 0, groups A and B received CsA vehicle and C and D received CsA (15 mg/kg) by daily gavage. Rats were bled on days -6, 0, 11, and 22 for serum bone gla protein (BGP), 1,25-(OH)2D, PTH, blood ionized Ca, and blood glucose determinations. Double tetracycline labeling was performed on days 9 and 20 for bone histomorphometry. After sacrifice on day 22, histomorphometric analysis was performed. Serum BGP, 1,25-(OH)2D, and PTH levels were significantly decreased in the diabetic alone (B) and diabetic plus CsA (D) groups and significantly increased in the CsA alone (group C). CsA alone (group C) induced cancellous bone loss by stimulated bone resorption. Cancellous bone loss in the diabetic alone rats (group B) was caused primarily by inhibited bone formation. No differences were found in cancellous bone mass, formation, or resorption parameters between diabetic alone (group B) and CsA-treated diabetic rats (group D). Neither CsA alone (group C) nor diabetic alone (group B) nor their combination affected cortical bone mass. CsA alone (group C) stimulated periosteal bone formation and endocortical bone resorption and inhibited endocortical formation, and diabetic alone (group B) inhibited both periosteal and endocortical bone formation. No parameters of tibial diaphyses in CsA-treated diabetic rats (group D) were different from diabetic alone. Thus the addition of CSA to the diabetic treated rats (group D) could not stimulate remodeling and appeared not to worsen significantly some of the alterations in bone formation and resorption. Possible explanations for this may be that CsA in vivo requires adequate levels of PTH, 1,25-(OH)2D, insulin, and perhaps growth factors to stimulate remodeling. The use of CsA in type I diabetic patients or in organ transplant recipients who remain diabetic after transplantation may in the short term not aggravate existing osteopenia based on these findings.

Animals↗
PubMed1994

Ultraviolet irradiation, although it activates the transcription factor AP-1 in F9 teratocarcinoma stem cells, does not induce the full complement of differentiation-associated genes.

Induction of differentiation of F9 teratocarcinoma stem cells by retinoic acid and cAMP has been shown to involve the activation of the transcription factor AP-1 (a heterodimer of the proto-oncogene products c-Fos and c-Jun); moreover, stable expression of either Fos or Jun drives F9 cells into differentiation. Phorbol ester tumor promoters and short-wave-length ultraviolet (uv) irradiation are efficient inducers of AP-1 activity in various differentiated cells, but it has been shown that phorbol esters do not induce AP-1 activity in undifferentiated F9 cells. We examine here whether uv irradiation induces AP-1 activity in these cells and drives F9 cells into differentiation. We show that uv induces, in contrast to phorbol esters, the formation of active AP-1 by activating transcription from the c-jun gene. Ultraviolet-induced AP-1 drives transcription from AP-1-dependent promoters coding for differentiation-associated proteins (such as urokinase and keratin 18). However, in uv-treated cells, these genes are activated earlier and to a greater extent than in cells treated with retinoic acid and cAMP. More importantly, uv, in contrast to retinoic acid and cAMP, does not induce the accumulation of collagen alpha 1 (IV) and laminin B1 RNA. Our data suggest that the c-jun gene in F9 cells is accessible to immediate activation, but that uv-induced AP-1 activation does not suffice to induce the full program of F9 cell differentiation.

Animals↗
PubMed1994

Pharmacological characterization of A2-adenosine receptors in guinea-pig ventricular cardiomyocytes.

The aim of the present study was to elucidate the question of whether cardiomyocytes possess stimulatory adenylyl cyclase-coupled A2-adenosine receptors and whether these receptors modify contractility. In isolated electrically driven ventricular cardiomyocytes from guinea-pig hearts the effects of the A2-adenosine receptor agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamide-adenos ine (CGS 21680C) alone and in the presence of isoprenaline on cAMP content and contractile response were investigated. In addition, we characterized these effects with selective A1- and A2-adenosine receptor antagonists [1,3-dipropyl-8-cyclopentylxanthine, DPCPX and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo-(1,5-c)quinazolin++ +-5-imine, CGS 15943A, respectively]. To investigate the signal transduction pathway, the influence of pertussis toxin, known to inhibit signal transducing GTP-binding proteins (Gi/o-proteins), on these effects was studied. CGS 21680C alone and in the presence of isoprenaline increased cAMP content concentration-dependently (0.1 nmol/l-10 mumol/l) to maximally 154% of control and 137% of isoprenaline value, respectively. In the presence of the A1-adenosine receptor antagonist DPCPX (0.3 mumol/l) or after pertussis toxin-pretreatment (18 micrograms/kg i.v. 24-26 h) the cAMP increase was further elevated. The A2-adenosine receptor antagonist CGS 15943A (0.01 mumol/l) abolished these effects, indicating that these effects are mediated by A2-adenosine receptors. The elevation in cAMP content was not accompanied by an increase in contractile response. However, in the presence of isoprenaline CGS 21680C reduced contractile response to 62% of the isoprenaline value. The A1-adenosine receptor antagonist DPCPX abolished the decrease in contractility, whereas the A2-adenosine receptor antagonist CGS 15943A did not effect contractility. Thus the reduction in contractility is mediated via cAMP-decreasing A1-adenosine receptors. The results provide evidence for the coexistence of cAMP-reducing A1- and cAMP-elevating A2-adenosine receptors on ventricular cardiomyocytes. Only stimulation of A1-adenosine receptors leads to a subsequent reduction in contractile response, whereas A2-adenosine receptors do not affect contractility.

Adenosine↗