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

Abstract

Background/Objective: Adenosine A1 receptors localized in the phrenic motoneurons (PMNs), where the axons of the descending bulbospinal respiratory make synaptic contacts, may be involved in theophylline- induced respiratory-related activity in rats. The objective of this study was to characterize the biochemical profiles of adenosine A., receptors in 2 groups of rats: (a) naive and (b) theophylline-treated (3-day oral administration).

Methods: Biochemical binding characteristics of adenosine A1 receptors in the C3 to C5 (PMN) of adult rats were assessed in naive (n = 6) and theophylline-treated animals (n = 6) using [3H]-DPCPX (10 pmol/L to 30 nmol/L), the specific adenosine A1 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 naive animals, the A1 receptor was characterized by a single binding site with Smax and Kd values of 256.00 ± 32.13 fmoi/mg protein and 2.89 ± 0.45 nmol/L, respectively. Analysis of the isotherm in theophylline-treated animals showed 1 site with Smax and Kd values of 219.00 ± 26.3 fmol/mg protein and 0.60 ± 0.21 nmol/L, respectively, and a second site characterized by Smax and Kd values of 492.6 ± 3.15 fmol/mg protein and 14.09 ± 2.06 n mol/L, respectively.

Conclusions: Theophylline administration revealed 2 binding sites on receptors (characterized by the specific adenosine A1 antagonist, [3H]-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.     

Views of general practitioners toward physiotherapy management of osteoarthritis—a qualitative study

ABSTRACT

Background: Osteoarthritis (OA) is a major cause of pain and physical disability, and general practitioners (GPs) are usually the first point of contact for patients. Physiotherapy has been shown as effective in the management of lower-limb OA. The aim was to explore the beliefs of GPs on the physiotherapy management of lower-limb OA in primary care. Methods: This is a qualitative study evaluating GP views about physiotherapy in Sheffield, South Yorkshire, UK. Participating GPs were recruited by systematic sampling, and invitation was given to GPs in 10 practices in the four localities in Sheffield. Semistructured interviews were completed and framework analysis was used to analyze the data. Results: Eight GPs were interviewed and six themes emerged from analysis of the data: perspective on OA, management strategy, views on patients, views on physiotherapy, working collaboratively, and suggestions for service improvements. GPs had a positive impression and knowledge of physiotherapy, but lacked understanding of the processes involved in treatment and limited awareness of clinical guidelines regarding the management of OA. Improvements in communication and collaborative working were critical issues suggested by the participants. Conclusion: This study found that GPs who were interviewed had a limited understanding on the role of physiotherapists and of clinical guidelines. Interprofessional communication was not as good as it should have been. A reconfiguration of the Sheffield musculoskeletal pathway may help achieve more effective collaborative working and a better outcome for patients.