Print ISSN: 2706-6207

Online ISSN: 2664-3154

Keywords : Ovine detrusor

The Effect of the P2X1 Receptor Antagonist MRS2159 on ATP- and EFS-Evoked Contractions of Isolated Ovine Detrusor Muscle Str

Mohammed H. Mahdi; Majid A. K. Lafi

Al- Anbar Medical Journal, 2016, Volume 13, Issue 1, Pages 57-73

Background: Overactive bladder (OAB) is a storage symptom complex often associated with detrusor over activity (DO). Antimuscarinic drugs still the mainstay treatment for OAB but the adverse effects limit their effectiveness, hence, alternatives are needed. Recently, β3 agonists have been introduced in clinical use for the treatment of OAB. At present, experimental search focusing on the potential use of P2X1 antagonist in DO.
Objectives: This study aims to investigate the possible existence of P2X1 purinoceptors and their interplay with β-Adrenoceptors in the ovine detrusor smooth muscle (DSM), and to examine the interaction of selected purinoceptors agonists and antagonists on models of voiding and non-voiding detrusor contractions.
Methods: In vitro experiments were performed on ovine detrusor muscle preparations in an organ bath containing Krebs solution. The contractile response of intact and denuded ovine DSM strips evoked by either 500µM adenosine 5’-triphosphate (ATP) or 10µM α,β-methylene ATP (α,β-meATP) or EFS was measured before and after the addition of 100µM MRS2159 (MRS) and 10µM isoprenaline (ISO) separately.
Results: ATP (500µM) and α,β-meATP (10 µM) effectively contracted the isolated ovine DSM producing a response consisting of two phases an initial transient rapid phasic contraction and a later slowly developing tonic contraction. MRS inhibited the phasic contractions evoked by 500µM ATP and 10Hz EFS in intact and denuded tissues, but it is completely abolished the contractions evoked by 10µM α,β-meATP. The cumulative administration of 50µM α,β-meATP abolished the phasic and tonic contractions evoked by ATP.
Conclusions: The contractile activity evoked by 10Hz EFS in the ovine DSM is largely mediated by the activation of P2X1 purinoceptors which are present abundantly in the ovine DSM and there is an intracellular inter talk between P2X1 purinoceptors and β-AR in the ovine DSM.

The Effect of Β3-Adrenoceptor Agonist (Brl37344) on Carbachol and Efs–Evoked Contractions of Isolated Ovine Detrusor Muscle Strip

Yousif Shabaan Dawood; Majid A. K. Lafi

Al- Anbar Medical Journal, 2016, Volume 13, Issue 1, Pages 37-46

Background: The concept of using β3-agonists in the treatment of overactive bladder with less side effects than the currently used anticholinergics, has been introduced recently.
Objectives: The aim of this paper to report the presence of β3-AR in the ovine detrusor muscle.
Methods: Appropriate sets of experiments using isolated ovine detrusor strips preparation. Cumulative effects of selected β-AR agonists including BRL37344 (BRL) were obtained on carbachol in presence and absence of propranolol and the β3-antagonist SR59230A, and EFS contracted strips.
Results: All agonists tested produced concentration-dependent relaxation, the rank order of their relaxing potency in the ovine detrusor muscle was isoprenaline (ISO)>BRL> dobutamine > salbutamol. Both ISO and BRL significantly suppressed 5Hz EFS contraction at a concentration had no significant effect on 40Hz EFS contraction.
Conclusion: It is concluded that β3-ARs are present abundantly in the ovine detrusor and the activation of which by the β-AR agonists suppresses the non-voiding detrusor contraction