Rosanda Buljubasich's Project

Purinergic neurotransmission in the guinea-pig prostate gland

The prostate is a male accessory gland. It sits beneath the urinary bladder where it surrounds the bladder neck and upper segment of the urethra in both the human and the guinea-pig. The principal function of the prostate is to produce and expel complex secretions into the male urogenital tract upon ejaculation, facilitating fertilization by increasing sperm motility and providing nourishment. Benign prostatic hyperplasia (BPH) is a result of androgen dependent growth in glandular and stromal elements of the gland as well as an increase in sympathetic tone to the prostatic smooth muscle. This increase in growth and tone of the gland with increasing age causes mechanical compression of the urethra and bladder neck resulting in urinary outflow obstruction. This leads to a number of lower urinary tract symptoms which are both irritative and obstructive. The nerves supplying the prostate are sympathetic and release adenosine 5’-triphosphate (ATP) and noradrenaline which act to elicit contraction of prostatic smooth muscle. The most successful class of drugs used to treat the symptoms of BPH in humans are the a₁-adrenoceptor antagonists. These drugs block the effects of noradrenaline at postjunctional a₁-adrenoceptors thereby reducing smooth muscle tone and alleviating urinary obstruction. However, adverse side effects associated with this line of treatment persist due to the presence of these receptors in the vascular system. This study will investigate the role of ATP and its breakdown products on smooth muscle contractility in the guinea-pig prostate. Given that humans and guinea-pigs exhibit similar age-related ultrastructural changes in prostatic stromal volume, the study of purinergic mechanisms in this animal model will provide us with a basis for predicting the suitability of specific purinergic target sites for therapy in disorders of the prostate.