ABSTRACT
The neurotransmitter molecule norepinephrine (noradrenaline) is located within densecore vesicles in sympathetic nerve terminals located within the prostate. The arrival of nerve impulses at the nerve endings provokes norepinephrine release by a process of fusion of these vesicles with the cell membrane of the nerve endings. Norepinephrine then diffuses across the synaptic gap to activate either α1-adrenoceptors, situated on the membrane of prostatic smooth muscle cells, or α2-adrenoceptors, located on the nerve terminal itself (Figure 15). These α2-adrenoceptors are autoregulatory in function and their blockade, by non-specific α-adrenoceptor blockers such as phenoxybenzamine, results in raised circulatory catecholamine levels with a consequent induction of tachycardia and palpitations. The α1-adrenoceptors located on the smooth muscle cell membrane are now known to consist of seven transmembrane domains and are linked intracellularly to a guanidine nucleotide binding protein (G protein) mechanism. Signal transduction results in G protein-linked activation of phospholipase C and the donation of a high-energy phosphate molecule from GTP. Signal amplification is accomplished by a molecular cascade, involving phosphotidylinositol and inositol triphosphate, which results in an influx of intracellular calcium, producing smooth muscle contractions as well as activation of protein kinase C, which, in turn, induces other intracellular metabolic responses13
(Figure 16). It has now been established that there are three subtypes of α1-adrenoceptor (Figure 17). These have been cloned14 and termed α1A, α1B and α1D. The α1A subtype appears to subserve mainly prostatic smooth muscle contraction; in contrast, the α1B variety is involved in the maintenance of vasoconstrictor tone. α1D Receptors are present in the detrusor muscle itself.
