scholarly journals In Vitro Safety Pharmacology Profiling of Topical α-Adrenergic Agonist Treatments for Erythema of Rosacea

Drugs in R&D ◽  
2018 ◽  
Vol 18 (1) ◽  
pp. 87-90 ◽  
Author(s):  
David Piwnica ◽  
Atul Pathak ◽  
Gregor Schäfer ◽  
James R. Docherty
Keyword(s):  
Adrenergic Agonist ◽  
Safety Pharmacology

Cytochemical Evidence for Presynatic β-Adrenergic Regulation of Secretion in the Developing Rat Submandibular Gland

1977 ◽  
Vol 35 ◽  
pp. 430-431
Author(s):  
L.S. Cutler
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Submandibular Gland ◽  
Neonatal Rat ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Parotid Glands ◽  
Adrenergic Agonist ◽  
Rat Submandibular Gland

Many studies previously have shown that the B-adrenergic agonist isoproterenol and the a-adrenergic agonist norepinephrine will stimulate secretion by the adult rat submandibular (SMG) and parotid glands. Recent data from several laboratories indicates that adrenergic agonists bind to specific receptors on the secretory cell surface and stimulate membrane associated adenylate cyclase activity which generates cyclic AMP. The production of cyclic AMP apparently initiates a cascade of events which culminates in exocytosis. During recent studies in our laboratory it was observed that the adenylate cyclase activity in plasma membrane fractions derived from the prenatal and early neonatal rat submandibular gland was retractile to stimulation by isoproterenol but was stimulated by norepinephrine. In addition, in vitro secretion studies indicated that these prenatal and neonatal glands would not secrete peroxidase in response to isoproterenol but would secrete in response to norepinephrine. In contrast to these in vitro observations, it has been shown that the injection of isoproterenol into the living newborn rat results in secretion of peroxidase by the SMG (1).

scholarly journals Metabolic effect of α-and the β-adrenergic stimulation of rat submaxillary gland in vitro

1976 ◽  
Vol 160 (3) ◽  
pp. 597-601 ◽  
Author(s):  
M P Thompson ◽  
D H Williamson
Keyword(s):  
Submaxillary Gland ◽  
Metabolic Effect ◽  
Metabolic Responses ◽  
Adrenergic Stimulation ◽  
Adrenergic Agonist ◽  
Presence And Absence ◽  
Stimulation Of

1. Incubation of submaxillary-gland slices with isoproterenol, a β-adrenergic agonist, stimulated glucose removal by 41% and decreased tissue [glucose 6-phosphate] by 50%. Propranolol blocked these effects of isoproterenol. 2. Phenylephrine, an α-adrenergic agonist, stimulated glucose removal by 35% and decreased tissue [glucose 6-phosphate] by 75%. In addition, phenylephrine also completely overcame the inhibition of pyruvate removal caused by acetoacetate metabolism and decreased tissue [atp] by 45%. Phentolamine blocked the effects of phenylephrine. 3. In contrast with β-adrenergic stimulation, α-adrenergic stimulation required exogenous Ca2+. 4. These results explain the different metabolic responses of the submaxillary gland to adrenaline in the presence and absence of exogenous Ca2+.

scholarly journals In vitro safety pharmacology evaluation of 2-hydroxybenzylamine acetate

2018 ◽  
Vol 121 ◽  
pp. 541-548 ◽  
Author(s):  
John C. Fuller ◽  
Lisa M. Pitchford ◽  
Ryan D. Morrison ◽  
J. Scott Daniels ◽  
Charles R. Flynn ◽  
...  
Keyword(s):  
Safety Pharmacology

Pharmacologic responsiveness of isolated single eccrine sweat glands

1981 ◽  
Vol 240 (1) ◽  
pp. R44-R51 ◽  
Author(s):  
K. Sato ◽  
F. Sato
Keyword(s):  
Dose Response ◽  
Dissociation Constants ◽  
Sweat Rate ◽  
Sweat Glands ◽  
Adrenergic Agonist ◽  
Beta Adrenergic ◽  
Adrenergic Agents ◽  
Eccrine Sweat Glands ◽  
Eccrine Sweat

Pharmacologic responsiveness of the eccrine sweat gland has never been studied under well-defined in vitro experimental conditions. Using isolated cannulated single monkey palm eccrine sweat glands, the dose response to both cholinergic and alpha- and beta-adrenergic agents and the effects of various antagonists on agonists were studied. The maximal sweat rate was highest after stimulation with cholinergic agonists, was lower with the beta-adrenergic agonist, and was least with the alpha-adrenergic agonist. Each secretory response was inhibited by its specific antagonist. Attempts to demonstrate the spare receptor, if any, by means of preincubation of the glands with N-(2-chlorethyl)dibenzylamine (Dibenamine) were unsuccessful. From the hyperbolic dose-response curves the values for KA and KB, dissociation constants for agonists and antagonists, respectively, were thus tentatively estimated according to Clark's classical receptor theory. Schild plots for each agonist-antagonist interaction produced straight lines with slopes of near unity, indicating the adequacy of the methodology. It was concluded that the isolated eccrine sweat glands retain their pharmacologic viability in vitro and show responsiveness to cholinergic as well as both alpha- and beta-adrenergic stimulations.

Regulation of ciliary beat frequency by autonomic mechanisms: in vitro

1988 ◽  
Vol 65 (4) ◽  
pp. 1895-1901 ◽  
Author(s):  
L. B. Wong ◽  
I. F. Miller ◽  
D. B. Yeates
Keyword(s):  
Laser Light ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Atropine Sulfate ◽  
Adrenergic Agonist ◽  
Muscarinic Cholinergic ◽  
Autonomic Receptors ◽  
Stimulation Of ◽  
Ciliary Beat

The ciliated epithelium of the mammalian trachea separates the neurohumoral milieu of the tissue from that of the environment of the airway lumen. To determine whether specific autonomic receptors regulating ciliary beat frequency (CBF) were located on mucosal or serosal sides, we measured CBF by heterodyne mode correlation analysis laser light scattering in bovine tracheal tissues mounted in a two-sided chamber. A beta 2-adrenergic agonist, fenoterol, at 10(-7) M, stimulated serosal CBF from 7.9 +/- 1.3 to 20.2 +/- 5.8 Hz (P less than 0.01) and mucosal CBF from 6.6 +/- 0.9 to 14.7 +/- 4.6 Hz (P less than 0.01). A muscarinic cholinergic agonist, methacholine, at 10(-7) M, increased mucosal CBF from 8.4 +/- 1.0 to 19.5 +/- 5.5 Hz (P less than 0.01) and serosal CBF from 8.0 +/- 0.9 to 15.4 +/- 5.0 Hz (P less than 0.01). The differences in stimulation of CBF on the mucosal and serosal sides between fenoterol and methacholine were significant (P less than 0.01). Studies in which these autonomic agonist stimulating effects were inhibited by their respective antagonists, propranolol and atropine sulfate, demonstrated that CBF can be regulated independently by mediators both in the submucosa and within the mucus lining.

Regulation of Trypanosoma cruzi infectivity by alpha- and beta-adrenergic agonists: desensitization produced by prolonged treatments or increasing agonist concentrations

Parasitology ◽  
1990 ◽  
Vol 100 (3) ◽  
pp. 429-434 ◽  
Author(s):  
A. Ayala ◽  
F. Kierszenbaum
Keyword(s):  
Trypanosoma Cruzi ◽  
Prolonged Exposure ◽  
Inhibitory Effect ◽  
Tissue Level ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
Alpha Adrenergic Agonist

SUMMARYWe previously reported that blood forms of Trypanosoma cruzi express alpha- and beta-adrenergic receptors and that binding of specific agonists to these receptors modifies the infective capacity of the parasite in vitro. The present study has revealed that the inhibitory effect of the beta-adrenergic agonist L-isoproterenol and the stimulatory effect of the alpha-adrenergic agonist L-phenylephrine are not produced when the parasite is subjected to prolonged exposure to otherwise effective doses of these agonists or when supraoptimal doses of these agonists are used. We refer to these phenomena as ‘desensitization’ because of their analogy with vertebrate cells becoming desensitized by prolonged exposure to, or relatively high concentrations of, adrenergic agonists. At a constant agonist concentration, T. cruzi desensitization was time-dependent and, when the time of parasite treatment with the agonists was not changed, the higher concentrations of the agonist tested were the most effective in producing desensitization. The reduced infectivity resulting from treatment with optimal doses of L-isoproterenol was accompanied by elevated levels of cyclic adenosine mono- phosphate (cAMP) which were not detectable when L-isoproterenol concentrations producing desensitization were used. This finding implicated cAMP as a likely second signal in the inhibitory mechanisms of this agonist. No significant change in cAMP was detectable in parasites treated with L-phenylephrine, leaving open the question about how optimal doses of this alpha-adrenergic agonist enhance T. cruzi infectivity. Parasite responsiveness to alpha- and beta-adrenergic agonists as well as the desensitization effects define a system which regulates infectivity and could be modified at the host tissue level by naturally occurring agonists.

β2-adrenergic agonist protects human endothelial cells from hypoxia/reoxygenation injury in vitro

2006 ◽  
Vol 34 (1) ◽  
pp. 165-172 ◽  
Author(s):  
Julien Pottecher ◽  
Gaëlle Cheisson ◽  
Olivier Huet ◽  
Christian Laplace ◽  
Eric Vicaut ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Endothelial Cells ◽  
Adrenergic Agonist ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

scholarly journals Catecholamines inhibit Ca2+-dependent proteolysis in rat skeletal muscle through β2-adrenoceptors and cAMP

2001 ◽  
Vol 281 (3) ◽  
pp. E449-E454 ◽  
Author(s):  
Luiz Carlos C. Navegantes ◽  
Neusa M. Z. Resano ◽  
Renato H. Migliorini ◽  
Ísis C. Kettelhut
Keyword(s):  
Skeletal Muscle ◽  
Extensor Digitorum Longus ◽  
Plasma Epinephrine ◽  
Dibutyryl Camp ◽  
Rat Skeletal Muscle ◽  
Adrenergic Agonist ◽  
Norepinephrine Content ◽  
Increased Activity ◽  
Dependent Pathway

Overall proteolysis and the activity of skeletal muscle proteolytic systems were investigated in rats 1, 2, or 4 days after adrenodemedullation. Adrenodemedullation reduced plasma epinephrine by 95% and norepinephrine by 35% but did not affect muscle norepinephrine content. In soleus and extensor digitorum longus (EDL) muscles, rates of overall proteolysis increased by 15–20% by 2 days after surgery but returned to normal levels after 4 days. The rise in rates of protein degradation was accompanied by an increased activity of Ca2+-dependent proteolysis in both muscles, with no significant change in the activity of lysosomal and ATP-dependent proteolytic systems. In vitro rates of Ca2+-dependent proteolysis in soleus and EDL from normal rats decreased by ∼35% in the presence of either 10−5 M clenbuterol, a β2-adrenergic agonist, or epinephrine or norepinephrine. In the presence of dibutyryl cAMP, proteolysis was reduced by 62% in soleus and 34% in EDL. The data suggest that catecholamines secreted by the adrenal medulla exert an inhibitory control of Ca2+-dependent proteolysis in rat skeletal muscle, mediated by β2-adrenoceptors, with the participation of a cAMP-dependent pathway.

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