Adrenergic receptors are expressed on the surface of inflammation-mediating cells, but their potential role in the regulation of the inflammatory response is still poorly understood. The objectives of this work were to study the effects of α2-adrenergic agonists on the inflammatory response in vivo and to determine their mechanism of action. In two mouse models of inflammation, zymosan air pouc...

PURPOSE Glaucoma is an optic neuropathy caused by the chronic and progressive death of retinal ganglion cells (RGCs), resulting in irreversible blindness. Ocular hypertension is a major risk factor, but RGC death often continues after ocular hypertension is normalized, and can take place with normal tension. Continuous RGC death was related in rodents and humans to the local upregulation of neu...

Despite years of drug development, electroconvulsive therapy (ECT) remains the most effective treatment for severe depression. The exact therapeutic mechanism of action of ECT is still unresolved and therefore we tested the hypothesis that the beneficial effect of ECT could in part be the result of increased noradrenergic neurotransmission leading to a decrease in α2-adrenoceptor binding. We ha...

The α2/δ1 and α(1)1.1 subunits are present at a 1:1 ratio in the dihydropyridine receptor (DHPR) from adult skeletal muscle. In contrast, during early myotube development α2/δ1 is present at higher levels than α(1)1.1 and localizes at the ends of the cells, suggesting that α2/δ1 may have a role independent from DHPRs. We sought to identify binding partners of α2/δ1 at a period when levels of α(...

Proton-coupled electron transfer (PCET) is a fundamental mechanism important in a wide range of biological processes including the universal reaction catalysed by ribonucleotide reductases (RNRs) in making de novo, the building blocks required for DNA replication and repair. These enzymes catalyse the conversion of nucleoside diphosphates (NDPs) to deoxynucleoside diphosphates (dNDPs). In the c...

Previous in vitro work on rabbit knee joint vessels showed that vasoconstrictor effects of nerve stimulation and administration of α-adrenoceptor agonists were mediated predominantly by α1-adrenoceptors5,9 The present experiments were performed to assess the nature of α-adrenoceptor subtypes within these blood vessels in vivo. Dose/response relationships for adrenaline and noradrenaline pr...

Nuclear import is required for communication between the cytoplasm and the nucleus and to enact lasting changes in gene transcription following stimuli. Binding to an Importin-α molecule in the cytoplasm is often required to mediate nuclear entry of a signaling protein. As multiple isoforms of Importin-α exist, some may be responsible for the entry of distinct cargoes rather than general nuclea...

Let α1 be a formula from N5 logic, and let α2 be the formula that is obtained from α1 by replacing conjunction, disjunction and implication by respectively a t-norm ⊗, a t-conorm ⊕ and an implicator →. Noting that V − 2 (w, a) ∈ {0, 1} and V + 2 (w, a) ∈ {0, 1} for all a ∈ At and w ∈ {h, t}, it follows easily from the definitions (17)–(23) that V1(w,α1) = 1 iff V2(w,α2) = [1, 1], V1(w,α1) = 1 i...

For many years, clonidine, an α2-adrenergic receptor (α2-AR) agonist, has been widely used as an analgesic adjuvant in perioperative conditions and pain therapy. Dexmedetomidine (DMET) is currently the most potent α2-AR agonist available and was first approved as a sedative agent for use in the intensive care unit. However, DMET has recently been investigated for its analgesic effects and has t...

There are four isoforms of the α subunit (α1-4) and three isoforms of the β subunit (β1-3) of Na,K-ATPase, with distinct tissue-specific distribution and physiological functions. α2 is thought to play a key role in cardiac and smooth muscle contraction and be an important target of cardiac glycosides. An α2selective cardiac glycoside could provide important insights into physiological and pharm...