Changes in the Biochemical Profiles of Mid-Cervically Located Adenosine A1 Receptors After Repeated Theophylline Administration in Adult Rats

Abstract

Background/Objective: Adenosine A 1 receptors localized in the phrenic motoneurons (PMNs), where the axons of the descending bulbospinal respiratory make synaptic contacts, may be involved in theophyllineinduced respiratory-related activity in rats. The objective of this study was to characterize the biochemical profiles of adenosine A 1 receptors in 2 groups of rats: (a) naïve and (b) theophylline-treated (3-day oral administration).Methods: Biochemical binding characteristics of adenosine A 1 receptors in the C3 to C5 (PMN) of adult rats were assessed in naïve (n ¼ 6) and theophylline-treated animals (n ¼ 6) using [ 3 H]-DPCPX (10 pmol/L to 30 nmol/L), the specific adenosine A 1 receptor antagonist in saturation-binding assays. Competition assays used theophylline as the competing ligand (20 mmol/L to 20 pmol/L), and protein concentration was determined with the Bradford assay using a range of standards (0.016-1.0 mg/mL). Results:In saturation-binding assays in naïve animals, the A 1 receptor was characterized by a single binding site with B max and K d values of 256.00 6 32.13 fmol/mg protein and 2.89 6 0.45 nmol/L, respectively. Analysis of the isotherm in theophylline-treated animals showed 1 site with B max and K d values of 219.00 6 26.3 fmol/mg protein and 0.60 6 0.21 nmol/L, respectively, and a second site characterized by B max and K d values of 492.6 6 3.15 fmol/mg protein and 14.09 6 2.06 n mol/L, respectively.Conclusions: Theophylline administration revealed 2 binding sites on receptors (characterized by the specific adenosine A 1 antagonist, [ 3 H]-DPCPX) located in the vicinity of phrenic motoneurons (C3-C5). Alteration of the receptor profiles after theophylline may underlie the respiratory-related actions of the drug. Spinal Cord Med. 2006;29:520-526 J

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

“…Notably, theophylline (Shahzadi et al, 2020;Shahzadi et al, 2022a), a naturally occurring methylxanthine, has found frequent therapeutic use in treating conditions such as asthma, respiratory deficits in premature infants, and chronic pulmonary obstructive disease (COPD). It also functions as a phosphodiesterase inhibitor (Ito et al, 2002;Saharan and Nantwi, 2006). Acefylline (Shahzadi et al, 2022b), a derivative of theophylline with pharmacological activity, serves various purposes, including bronchodilation, heart stimulation, diuresis, smooth muscle relaxation, antimicrobial and antituberculosis properties, and antiinflammatory effects (Foppoli et al, 2007;Mangasuli et al, 2018;Gopinatha et al, 2020;Shahzadi et al, 2020;Shahzadi et al, 2022a;Montaño et al, 2022), as illustrated in Figure 1.…”