The autonomic and sensory innervation of the smooth muscle of the prostate gland: a review of pharmacological and histological studies.

1. We review literature demonstrating (a) the presence and (b) the actions of substances that mediate or modify neuroeffector transmission to the smooth muscle of the prostrate stroma of a number of species including man. 2. In all species studied prostatic stroma, but not secretory acini, receives rich noradrenergic innervation. Stimulation of these nerves causes contractions of prostate smooth muscle that are inhibited by guanethidine and by alpha1-adrenoceptor antagonists that probably act at the alpha1L-adrenoceptor. Such actions underlie the clinical use of alpha1-adrenoceptor antagonists in benign prostatic hyperplasia (BPH). 3. Acetylcholinesterase-positive nerves innervate prostatic stroma as well as epithelium. Atropine reduces nerve-mediated contractions of stromal muscle in the rat, guinea-pig and rabbit. M1, M2 and M3 muscarinic receptors have been implicated in eliciting or facilitating contraction in the prostate from guinea-pig, dog and rat, respectively. 4. Adenine nucleotides and nucleosides, nitric oxide (NO), opioids, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) may act as co-transmitters or modulators in autonomic effector nerves supplying prostate stroma. Adenosine inhibits neurotransmission to the rat prostate, and NO is inhibitory in prostate from human, rat, rabbit, pig and dog. The activity of peptides present in the relatively sparse sensory innervation of the prostate exhibits species variation, but, when effective, calcitonin gene-related peptide is inhibitory while tachykinins are stimulant. The roles of NPY and VIP in modulating stromal contractility remain unclear. 5. Taken together the current literature indicates that, in addition to noradrenaline, other neurotransmitters and neuromodulators may regulate the tone of prostatic smooth muscle. Whether drugs that mimic or modify their actions might be useful in providing symptomatic relief of the urinary symptoms associated with BPH remains to be established.