Synthesis of 2-amino-3-heteroaroylthiophenes and evaluation of their activity as potential allosteric enhancers at the human A1 receptor.

2-Amino-3-benzoylthiophenes are allosteric enhancers of agonist binding to the adenosine A(1) receptor. New compounds bearing an heteroaroyl instead of the benzoyl moiety at the 3-position of the thiophene were synthesized. The phenyl ring was replaced with heterocycles that possess heteroatoms able to form hydrogen bonds (2-furanyl, 2-benzofuranyl, 2-pyridinyl in compounds 2-13) or with a thienyl moiety as isoster of the phenyl ring (2-thienyl, 3-thienyl and 5-halo-2-thienyl in compounds 14-29).

Alteration of A(3) adenosine receptors in human neutrophils and low frequency electromagnetic fields.

The present study was designed to evaluate the binding and functional characterization of A(3) adenosine receptors in human neutrophils exposed to low frequency, low energy, pulsing electromagnetic fields (PEMFs). Great interest has grown concerning the use of PEMF in the clinical practice for therapeutic purposes strictly correlated with inflammatory conditions. Saturation experiments performed using the high affinity and selective A(3) adenosine antagonist 5N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2-(2-furyl)pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine ([3H]-MRE 3008F20) revealed a single class of binding sites with similar affinity in control and in PEMF treated human neutrophils (K(D)=2.

Synthesis and biological effects of novel 2-amino-3-naphthoylthiophenes as allosteric enhancers of the A1 adenosine receptor.

The current study describes the synthesis and biological evaluation of a novel series of 2-amino-3-naphthoylthiophenes, with variable modifications at the 4- and 5-position of the thiophene as well as the naphthoyl ring. Allosteric enhancer activity was measured in several ways: (1) evaluating the effect on forskolin-stimulated cAMP accumulation in the presence of an A(1)-adenosine agonist (CPA) in Chinese hamster ovary (CHO) cells expressing the cloned human A(1)-adenosine receptor (hA(1)AR); (2) ability of these compounds to displace the binding of [(3)H]DPCPX, [(3)H]ZM 241385, and [(3)H]MRE 3008F20 to the ligand binding site of CHO cells expressing the hA(1), hA(2A), and hA(3) adenosine receptors, respectively; (3) effect on the binding of [(3)H]CCPA to membranes from CHO cells expressing hA(1)AR, to rat brain and human cortex membrane preparations containing native adenosine A(1) receptors; (4) kinetics of the dissociation of [(3)H]CCPA from CHO-hA1 membranes. The pharmacological assays compared the various activities to that of the reference compound PD 81,723 (compound 1).

Effects of doxazosin and propranolol on A2A adenosine receptors in essential hypertension.

A2A adenosine receptors inhibit neutrophil adhesion and superoxide anion generation. The aim of the present study was to evaluate the effect of antihypertensive treatment with doxazosin or propranolol on the binding and functional parameters of A2A adenosine receptors of lymphocytes and neutrophils in essential hypertensive patients. Two groups of previously untreated, essential hypertensive patients were studied.

Effect of low frequency electromagnetic fields on A2A adenosine receptors in human neutrophils.

The present study describes the effect of low frequency, low energy, pulsing electromagnetic fields (PEMFs) on A2A adenosine receptors in human neutrophils. Saturation experiments performed using a high affinity adenosine antagonist [3H]-ZM 241385 revealed a single class of binding sites in control and in PEMF-treated human neutrophils with similar affinity (KD=1.05+/-0.