Contractile properties of human prostate adenomas and the development of infravesical obstruction

Abstract

The contractile response of human prostate adenomas to KCl, phenylephrine (alpha 1 adrenergic agonist), UK 14304 (alpha 2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine-induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine-induced contractions by prazosin was 3.2 nM, confirming that phenylephrine-induced contraction in the human prostate is mediated by the alpha 1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha 2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma.

Contractions of the Mouse Prostate Elicited by Acetylcholine Are Mediated by M3 Muscarinic Receptors

“…Unlike in the mouse prostate, the cholinergic component of nerve-mediated contraction in the human prostate is small compared with the adrenergic response (Caine et al, 1975;Hedlund et al, 1985;Gup et al, 1989;Kester et al, 2003). However, another study has observed an adreno-muscarinic synergy in contraction of the human prostate (Roosen et al, 2009).…”

The Residual Nonadrenergic Contractile Response to Nerve Stimulation of the Mouse Prostate Is Mediated by Acetylcholine but Not ATP in a Comparison with the Mouse Vas Deferens

“…Some studies have also reported that muscarinic receptor agonists mediate contraction in the human prostate (Caine et al, 1975;Gup et al, 1989;Kester et al, 2003), whereas in other human studies no contraction was observed (Hedlund et al, 1985). When observed, cholinergic receptor agonist-mediated contraction seems to be localized to the prostatic capsule.…”

Morning vs evening dosing with doxazosin in benign prostatic hyperplasia: efficacy and safety

“…3 It is thought that the symptoms of BPH result both from mechanical obstruction of the urethra by the enlarging prostate, and a dynamic component which results from sympathetic stimulation of smooth muscle tone. Blocking the a 1 -adrenergic receptors in the prostate results in relaxation of the smooth muscle, decreasing the dynamic component, and contributing to improvements in the symptoms of BPH.…”