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Mesial Temporal Lobe Epilepsy (MTLE) Drug-Refractoriness Is Associated With P2X...

Guerra Leal, Bárbara; Barros-Barbosa, Aurora; Ferreirinha, Fátima; Chaves, João; Rangel, Rui; Santos, Agostinho; Carvalho, Cláudia

Objective: ATP-gated ionotropic P2X7 receptors (P2X7R) actively participate in epilepsy and other neurological disorders. Neocortical nerve terminals of patients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) express higher P2X7R amounts. Overexpression of P2X7R bolsters ATP signals during seizures resulting in glial cell activation, cytokines production, and GABAergic rundown with unre...


Opposing Effects of Adenosine and Inosine in Human Subcutaneous Fibroblasts May...

Herman-de-Sousa, Carina; Pinheiro, Ana Rita; Paramos-de-Carvalho, Diogo; Costa, Maria Adelina; Ferreirinha, Fátima; Magalhães-Cardoso, Teresa

Human subcutaneous fibroblasts (HSCF) challenged with inflammatory mediators release huge amounts of ATP, which rapidly generates adenosine. Given the nucleoside's putative relevance in wound healing, dermal fibrosis, and myofascial pain, we investigated the role of its precursor, AMP, and of its metabolite, inosine, in HSCF cells growth and collagen production. AMP (30 µM) was rapidly (t½ 3 ± 1 min) dephosphor...


β3 Adrenoceptor-induced cholinergic inhibition in human and rat urinary bladder...

Silva, Isabel; Magalhães‐Cardoso, M. Teresa; Ferreirinha, Fátima; Moreira, Sílvia; Costa, Ana Filipa; Silva, Diogo; Vieira, Cátia; Silva-Ramos, Miguel

Background and purpose: The mechanism by which β3 receptor agonists (e.g. mirabegron) control bladder overactivity may involve adenosine release from human and rat detrusor smooth muscle. Retrograde activation of adenosine A1 receptors reduces ACh release from cholinergic bladder nerves. β3 -Adrenoceptors usually couple to adenylyl cyclase. Here we investigated, which of the cAMP targets, protein kinase A or th...


Diabetic rats lose A2A receptor-mediated facilitation of ileal myenteric cholin...

Monteiro, Salomé Gonçalves; Cardoso, Maria Teresa Magalhães; Ferreirinha, Fátima; Henriques, Vanessa Mendes; Sá, Paulo Correia de

Enteric dysmotility is a long-term complication of Diabetes mellitus that causes significant discomfort in 76% of diabetic outpatients. Knowing that purines may be involved in synaptic transmission modifications in the CNS of diabetic rats, we decided to investigate if purinergic dysfunction could also play a role in diabetic enteric neuropathy in rats.


Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive ...

Certal, Mariana; Vinhas, Adriana; Pinheiro, Ana Rita; Ferreirinha, Fátima; Barros-Barbosa, Aurora Raquel; Silva, Isabel; Costa, Maria Adelina

During myocardial ischemia and reperfusion both purines and pyrimidines are released into the extracellular milieu, thus creating a signaling wave that propagates to neighboring cells via membrane-bound P2 purinoceptors activation. Cardiac fibroblasts (CF) are important players in heart remodeling, electrophysiological changes and hemodynamic alterations following myocardial infarction. Here, we investigated th...


Bradykinin-induced Ca2+ signaling in human subcutaneous fibroblasts involves AT...

Pinheiro, Ana Rita; Paramos-de-Carvalho, Diogo; Certal, Mariana; Costa, Cristina; Magalhães-Cardoso, Maria Teresa; Ferreirinha, Fátima

Chronic musculoskeletal pain involves connective tissue remodeling triggered by inflammatory mediators, such as bradykinin. Fibroblast cells signaling involve changes in intracellular Ca2+ ([Ca2+]i). ATP has been related to connective tissue mechanotransduction, remodeling and chronic inflammatory pain, via P2 purinoceptors activation. Here, we investigated the involvement of ATP in bradykinin-induced Ca2+ sign...


Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin...

Pinheiro, Ana Rita; Paramos-de-Carvalho, Diogo; Certal, Mariana; Costa, Maria Adelina; Costa, Cristina; Magalhães-Cardoso, Maria Teresa

Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a ris...


Molecular diagnosis of Huntington disease in Portugal : implications for geneti...

Costa, Maria do Carmo; Magalhães, Paula; Ferreirinha, Fátima; Guimarães, Laura; Januário, Cristina; Gaspar, Isabel; Loureiro, Leal; Vale, José

Huntington disease (HD) is a eurodegenerative, autosomal dominant disorder of late-onset, caused by the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history. A total of 338 genetic te...


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