Drugs online research references
medizin.uni-leipzig.de
OBJECTIVE: We studied the ability of norepinephrine and of other catecholamines to affect the proliferation of cardiac fibroblasts isolated from adult rat hearts. Furthermore, we investigated the possible adrenergic receptor involved in this process. METHODS: Norepinephrine (NE), phenylephrine (PE), isoproterenol (ISO), forskolin (FO), epidermal growth factor (EGF), platelet-derived growth factor AA (PDGF-AA) and specific inhibitors of the alpha(1)-, alpha(2)-, beta(1)- and beta(2)-adrenoceptors and of the protein kinase A (PKA) were applied to cardiac fibroblasts in culture. Cell number was measured by use of a Coulter Counter. Activation of the cAMP response element binding protein (CREB) was measured by Western blotting and subsequent use of a phospho-specific antibody. Activation of the p42- and the p44-mitogen activated protein kinase (p42/p44(MAPK)) was assessed by detection of phosphorylation shifts and by incorporation of 32P-labelled phosphate into myelin basic protein. RESULTS: Fibroblasts isolated from hearts of adult rats were grown in 10% serum-containing media which induced an increase in cell number by 94%. After 48 h, treatment with 10 microM NE caused an even greater increase in cell number by 222%, i.e. another 128% (comitogenic effect). In contrast, NE alone had no effect on the growth of serum-deprived cells. EGF and PDGF-AA did not replace serum as the basic mitogen. After addition of NE to proliferating cells under serum conditions, there was a rapid, time-dependent significant activation of the p42/p44(MAPK) and of CREB for up to 60 and 120 min, respectively. In both cases, the maximum of activation was reached after 5 min. Application of FO (0.1-20 microM) caused a strong activation of CREB, while no increase in the phosphorylation of the p42/p44(MAPK) was detected. Treatment with 20 microM FO led to an identical increase in cell number as application of NE. Specific blockade of PKA with RpcAMPS prevented the activation of CREB and also the comitogenic effect of FO as well as of NE. The alpha- and beta-adrenergic receptor blocker carvedilol (10 microM) normalized all NE-induced effects. Prazosin and yohimbine, inhibitors of alpha(1)- and alpha(2)-adrenoceptor activation, respectively, did not influence the NE-evoked increase in cell number. In contrast, the non-selective beta-adrenoceptor blocker propranolol (1 microM) completely suppressed the comitogenic effect of NE. A similar effect was obtained with the specific beta(2)-adrenoceptor blocker ICI 118,551 (5 microM), while the beta(1)-adrenoceptor blocker metoprolol did not influence the increase in cell number. CONCLUSIONS: NE elicits a comitogenic effect on cultured rat cardiac fibroblasts which is prevented by beta(2)-adrenergic blockade. The activation of CREB contributes to the increase in proliferation. The p42/p44(MAPK) which was also found to be activated by NE might as well be involved in the regulation of the comitogenic effect.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054474&dopt=Abstract
J Pharmacol Exp Ther. 1997 Dec;283(3):1389-95.
Abnormality in plasma catecholamines and myocardial adrenoceptors in cardiomyopathic BIO 53.58 Syrian hamsters and improvement by metoprolol treatment.
Yamada S, Ohkura T, Yamadera T, Ito O, Kimura R, Nozawa Y, Hayashi S, Miyake H.
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Taiho Pharmaceutical Company, Ltd., Tokushima, Japan.
The catecholaminergic neuronal activity and the densities of alpha-1 and beta adrenoceptors and angiotensin II receptors were simultaneously determined in BIO 53.58, a model of idiopathic dilated cardiomyopathy, and F1B control hamsters. Further, we examined the effect of repeated p.o. administration of metoprolol on these biochemical parameters. Compared with F1B control hamsters, there was a significant decrease in Bmax of specific binding of both (-)-[125I]iodocyanopindolol and [3H]prazosin with a marked elevation of plasma catecholamine (mainly norepinephrine and epinephrine) concentrations, in BIO 53.58 hamsters at 11 and 18 weeks of age (severe cardiomyopathic stage), but not at 5 weeks of age. On the other hand, the Bmax value of myocardial [125I]angiotensin II binding in BIO 53.58 hamsters was almost identical to that in F1B hamsters. These results suggest a development of down-regulation of myocardial beta and alpha-1 adrenoceptors because of an increased catecholaminergic neuronal activity with aging in BIO 53.58 hamsters. Repeated p.o. administration of a relatively low dose (1 mg/kg/day) of metoprolol for 7 weeks in 11-week-old BIO 53.58 hamsters caused a significant increase of myocardial (-)-[125I]iodocyanopindolol binding sites with a marked reduction in plasma catecholamine levels; this indicated a significant recovery to the F1B levels. The improvement of these biochemical parameters by metoprolol treatment was also accompanied by a significant decrease in the fibrosis in the heart in BIO 53.58 hamsters. These data suggest that catecholaminergic neurons and adrenoceptors play a part in the development of heart failure in idiopathic dilated cardiomyopathy. Consequently, the present study may provide a further pharmacological basis for the use of beta-1 adrenoceptor antagonists in patients with idiopathic dilated cardiomyopathy.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9400015&dopt=Abstract
J Cardiovasc Pharmacol. 1994 Mar;23(3):492-500.
Interactions of a novel catecholamine, GP-2-128, with adrenoceptors.
Abou-Mohamed G, Caldwell RW, Carrier GO, Elmazar MM, Tuttle RR.
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
GP-2-128 is a novel catecholamine designed for transdermal iontophoretic delivery in patients with limited mobility to prevent deconditioning and muscular wasting. We characterized the interactions of this agent with alpha- and beta-adrenoceptors in vitro. In electrically stimulated rat left atria, GP-2-128 produced a concentration-dependent increase in contractile force. pD2 values for GP-2-128, isoproterenol (ISO), and dobutamine (DOB) were 10.6 +/- 0.12, 8.55 +/- 0.02, and 7.0 +/- 0.20, respectively. Metoprolol caused a shift in the concentration-effect curves for the three agonists. In spontaneously beating rat right atria, pD2 values of GP-2-128, ISO, and DOB are 10.4 +/- 0.24, 8.82 +/- 0.18, and 6.92 +/- 0.18, respectively. The affinity constant (KA) of GP-2-128, ISO, and DOB for cardiac beta 1-adrenoceptors was determined by competition binding assays to be 8.09, 6.04 and 4.49, respectively. In guinea pig trachea precontracted with histamine, GP-2-128 and ISO produced a concentration-dependent relaxation. pD2 values were 10.0 +/- 0.1 and 8.2 +/- 0.1, respectively. DOB was more potent than GP-2-128 in contracting isolated rat aortic rings (alpha 1 effect) and in displacing [3H]rauwolscine (alpha 2 effect). We also studied the interactions of GP-2-128 and ISO with the atypical beta-adrenoceptors (beta 3) in guinea pig ilea and rat and hamster adipocytes. Both agents inhibited twitches produced by transmural nerve stimulation in the presence of 10(-5) M nadolol. The EC30 for GP-2-128 and ISO at this atypical receptor site were 4.25 x 10(-10) and 5.05 x 10(-8) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7515996&dopt=Abstract
online pharmacies ||
Hair Million herbal formula for hair loss and hair growth ||
Amoxicillin ||
Tramadol ||
Paxil ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Zithromax ||
online pharmacy ||
Antibiotics and prescription medications online literature ||
Antibiotics