Effects of α 1 -adrenoceptor modulation, using tamsulosin, on spontaneous activity in the guinea pig prostate gland

B Chakrabarty, A Dey, M Lam, S Ventura, B Exintaris. Monash Institute of Pharmaceutical Sciences, Drug Discovery Biology 3052, Australia

Introduction: Changes to α1-adrenoceptors and spontaneous activity contribute to an increase in smooth muscle tone with age, a major component that is associated in the aetiology of Benign Prostatic Hyperplasia (BPH).

Objectives: To examine the effects of α1-adrenoceptor antagonist, tamsulosin, on spontaneous contractile and spontaneous electrical activity in the prostate gland of adult (5-8 months) and ageing (>9 months) guinea pigs.

Methods: Conventional tension recording and intracellular microelectrode electrophysiology techniques were used.

Results: Tamsulosin (0.1 nM, 20 minutes) reduced spontaneous contractile activity relative to control in adult and ageing guinea pigs, from 2.6±0.3 min-1 to 1.1±0.2 min-1 (n=5, P<0.01) and 2.8±0.5 min-1 to 1.3±0.4 min-1 (n=5, P<0.01), respectively. Spontaneous contractile activity was significantly more reduced in ageing guinea pigs (ANOVA, P<0.001), in comparison to adult guinea pigs (ANOVA, P<0.01).Similarly, spontaneous electrical slow wave activity was significantly more reduced in ageing guinea pigs (ANOVA, P<0.05), in comparison to adult guinea pigs (ANOVA, P>0.05). Tamsulosin (0.3 nM, 20 minutes) abolished spontaneous contractions in 55% of preparations in adult guinea pigs (n=9). In contrast, spontaneous contractile activity was significantly reduced relative to control in ageing guinea pigs, from 2.7±0.6 min-1 to 1.4±0.4 min-1 (n=5, P<0.05). Spontaneous electrical activity was significantly reduced from 7.4±0.4 min-1 to 6.2±0.8 min-1 (n=6, P<0.05), resulting in the alteration of time course frequency to display cyclical intermittent burst and lag phase intervals in 100% of cells in adult guinea pigs. Spontaneous electrical activity was also significantly more reduced in adult guinea pigs (ANOVA, P<0.5), in comparison to ageing guinea pigs (ANOVA, P>0.05).

Discussion: Tamsulosin reduces spontaneous contractions and the underlying spontaneous electrical activity, and has different effects on adult and ageing guinea pigs at different concentrations. This modulation in spontaneous stromal excitability and downstream cellular mechanisms may be resulting in the increased clinical efficacy associated with tamsulosin. These specific underlying mechanisms may be therapeutically targeted with the development of new, novel drugs to potentially treat BPH.