Identification and coupling to adenylate cyclase of three different [3H]CGP 12177 binding sites in Caco-2 cell membranes

Badino, P.; Angelis, De; Odore, R.; Belloli, Chiara; Stammati, Annalaura; Zucco, Flavia

doi:10.1006/phrs.2001.0802

Cited by 4 publications

(5 citation statements)

References 27 publications

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“…Particularly, selective b-AR binding assays revealed the presence of a homogeneous population of b 2 -AR. The binding assays performed using higher concentrations of labelled CGP12177 allowed to discriminate an atypical b-AR (b 3 -AR) subtype, as previously demonstrated (Re et al, 2001a). Scatchard plots were linear (r > 0.9) and saturation curves indicated that the concentrations of (-)[ 3 H]CGP12177 and [ 3 H]prazosin were able to saturate the receptor populations expressed in prostatic tissue (data not shown).…”

Section: Adrenergic Receptor Assayssupporting

confidence: 66%

“…Particularly, selective β ‐AR binding assays revealed the presence of a homogeneous population of β 2 ‐AR. The binding assays performed using higher concentrations of labelled CGP12177 allowed to discriminate an atypical β ‐AR ( β 3 ‐AR) subtype, as previously demonstrated (Re et al. , 2001a).…”

Section: Resultsmentioning

confidence: 60%

“…The concentrations of β 3 ‐ARs were measured using a higher concentration range of (‐)[ 3 H]CGP12177 (3–20 n m ), in the presence or in the absence of 0.5 m m propranolol to assess the nonspecific binding (Sillence et al. , 1993; Re et al. , 2001a).…”

Section: Methodsmentioning

confidence: 99%

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Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

Barbero

Badino

Odore

et al. 2006

Vet Pharm & Therapeutics

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Mepartricin is a semi-synthetic macrolide antibiotic developed as a drug for the treatment of benign prostatic hyperplasia (BPH) in human patients. In the present study, aged rats are used as an experimental model to evaluate the effects of mepartricin on circulating hormone concentrations and prostate receptor concentrations, to compare these possible effects with clinical findings observed in long-term treated dogs. Fifty-six aged male rats were randomly divided into four experimental groups treated orally with 0 (group 1), 2 mg (group 2), 5 mg (group 3) and 20 mg (group 4) mepartricin/kg of body weight. for 28 days respectively. Serum oestradiol and testosterone concentrations were measured by radio-immune-assays methods. Binding assays were used to measure the prostate concentrations of oestrogen receptors (ER), androgen receptors (AnR), alpha(1)-adrenergic receptor (alpha(1)-AR), and beta-adrenerergic receptor (beta-AR) subtypes. Mepartricin induced a significant reduction of prostate weight and serum oestradiol concentrations. Serum testosterone concentrations were unaffected. The treatment induced a significant down-regulation of ER concentrations (P < 0.05) and a significant up-regulation of AnR (P < 0.05) in rat prostate. Mepartricin induced a significant (P < 0.05) dose-dependent up-regulation of alpha(1)-AR and beta(2)-AR. In contrast, the concentration of beta(3)-ARs was significantly decreased (P < 0.05) in treated animals. The increase in prostate beta(2)-AR concentrations observed in subjects treated with mepartricin may be a favourable element in the evolution of BPH, because of the role exerted by these receptors in the control of prostatic smooth muscle relaxation. Curiously, beta(3)-AR concentrations were significantly reduced in treated animals. Data collected suggest that the prostatic beta-AR expression might be strongly influenced by oestrogen deprivation (mepartricin treatment); therefore, the combination of oestrogen suppression (mepartricin) and adrenergic suppression (alpha(1)-AR blockers) may be proposed as a possible nonhormonal therapeutic strategy for the treatment of benign prostatic hyperplasia in dogs.

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Section: Adrenergic Receptor Assayssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 60%

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Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

Barbero

Badino

Odore

et al. 2006

Vet Pharm & Therapeutics

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“…Moreover, β 2 -AR agonists activate CFTR in intestinal organoids through cAMP signaling ( Vijftigschild et al, 2016 ), and optimal activity of CFTR in Caco-2 human colon carcinoma cells is dependent on the presence of glucose ( Mailleau et al, 1998 ). Coupling of the β 2 - AR to adenylate cyclase has been demonstrated in Caco-2 cell membranes based on the increase in cAMP level upon addition of different agonists ( Re et al, 2001 ). Evidence was reported for an electrogenic response mediated by β 2 -ARs located in the basolateral membrane of distal colonic brush border basolateral membranes mounted in Ussing chambers ( Zhang et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

The β2-adrenergic receptor in the apical membrane of intestinal enterocytes senses sugars to stimulate glucose uptake from the gut

Paulussen

Kulkarni

Stolz

et al. 2023

Front. Cell Dev. Biol.

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The presence of sugar in the gut causes induction of SGLT1, the sodium/glucose cotransporter in intestinal epithelial cells (enterocytes), and this is accompanied by stimulation of sugar absorption. Sugar sensing was suggested to involve a G-protein coupled receptor and cAMP - protein kinase A signalling, but the sugar receptor has remained unknown. We show strong expression and co-localization with SGLT1 of the β2-adrenergic receptor (β2-AR) at the enterocyte apical membrane and reveal its role in stimulating glucose uptake from the gut by the sodium/glucose-linked transporter, SGLT1. Upon heterologous expression in different reporter systems, the β2-AR responds to multiple sugars in the mM range, consistent with estimated gut sugar levels after a meal. Most adrenergic receptor antagonists inhibit sugar signaling, while some differentially inhibit epinephrine and sugar responses. However, sugars did not inhibit binding of I125-cyanopindolol, a β2-AR antagonist, to the ligand-binding site in cell-free membrane preparations. This suggests different but interdependent binding sites. Glucose uptake into everted sacs from rat intestine was stimulated by epinephrine and sugars in a β2-AR-dependent manner. STD-NMR confirmed direct physical binding of glucose to the β2-AR. Oral administration of glucose with a non-bioavailable β2-AR antagonist lowered the subsequent increase in blood glucose levels, confirming a role for enterocyte apical β2-ARs in stimulating gut glucose uptake, and suggesting enterocyte β2-AR as novel drug target in diabetic and obese patients. Future work will have to reveal how glucose sensing by enterocytes and neuroendocrine cells is connected, and whether β2-ARs mediate glucose sensing also in other tissues.

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“…In recent years, the research has been focused on compounds that are toxic for the gastro-intestinal tract, and also investigating their absorption, by using in vitro intestinal models. This non-animal-based approach, integrating toxicodynamics and biokinetics, should lead to the development of a strategy for measuring the real exposure of cells to chemicals and to the prediction of biokinetics in humans (38)(39)(40).…”

Section: : Annalaura Stammati (Italy) -For In Vitro Studies On Thmentioning

confidence: 99%

The Tenth Anniversary of the Björn Ekwall Memorial Foundation

2011

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The Björn Ekwall Memorial Foundation (BEMF) was initiated by the Scandinavian Society for Cell Toxicology in 2001, to honour the memory of Dr Björn Ekwall (1940–2000) and to establish a prize, the Björn Ekwall Memorial Award. The prize is awarded to scientists who have significantly contributed to the field of cell toxicology, and whose work is contributing toward the replacement of animal experiments by alternative toxicity tests. Over the past 10 years, the Björn Ekwall Memorial Award has been presented annually. Björn Ekwall, an outstanding Swedish cell toxicologist, was one of the pioneers in the development and application of alternative methods to animal tests in toxicology. All his scientific work was devoted to in vitro toxicology, and in particular, to the use of cultured human cells for the screening of toxic chemicals. In the middle of the 1980s, he initiated the international Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) project, to evaluate the usefulness of in vitro tests for the estimation of human acute systemic toxicity. To prove his “basal cytotoxicity concept”, he established the MEMO database, in which data on the acutely toxic human blood concentrations of drugs and chemicals were collated from the literature and from clinical studies. He also initiated another project, Evaluation-Guided Development of In Vitro Toxicity and Toxicokinetic Tests (EDIT). The ideas from the EDIT project, together with those from the MEIC project, became the basis for today's international EU projects, e.g. ACuteTox, Sens-it-iv and ReProTect. In this article, 10 years after the start of the BEMF, the scientific achievements of each of the award winners in the field of in vitro toxicology are presented, together with a brief synopsis of their careers.

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Identification and coupling to adenylate cyclase of three different [3H]CGP 12177 binding sites in Caco-2 cell membranes

Cited by 4 publications

References 27 publications

Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

Mepartricin long‐term administration regulates steroid hormone and adrenergic receptor concentrations in the prostate of aged rats

The β2-adrenergic receptor in the apical membrane of intestinal enterocytes senses sugars to stimulate glucose uptake from the gut

The Tenth Anniversary of the Björn Ekwall Memorial Foundation

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