Effects of muscarinic agonists in the guinea-pig prostate

1. The contractile response to transmural stimulation of the guinea-pig prostate is largely due to activation of noradrenergic neurons but there is a small contribution from cholinergic neurons. Carbachol and acetylcholine have been reported to act via muscarinic M(1) cholinoceptors to facilitate contractions produced by neuronal stimulation of the tissue. This action of cholinomimetics was further investigated in isolated ventral lobes of the prostate. 2. Oxotremorine-M, bethanecol, pilocarpine, xanomeline and McN-A-343 produced facilitation of the response to transmural stimulation of the prostate. When carbachol was applied as the first agonist, the facilitatory response to the latter four agonists above was absent or reduced, compared with the effect observed when the other agonist was applied first, indicating that the effect of these agonists is readily desensitized. Only oxotremorine-M was unaffected by prior exposure of the tissue to carbachol. When applied first, pilocarpine and xanomeline produced a smaller degree of facilitation than carbachol indicating they were partial agonists for the effect. The facilitation produced by McN-A-343, when applied as the first agonist, was variable. In some preparations the facilitation was less than that of carbachol but in others it exceeded that produced by a subsequent application of carbachol. 3. The release of endogenous choline from the prostate was measured at rest and during transmural stimulation using a chemiluminescent technique. A statistically significant negative correlation existed between pmol mg(-1) of endogenous choline released during transmural stimulation and the mass of the ventral lobe of the prostate. As the guinea-pig prostate is known to undergo postpubertal stromal hypertrophy the finding suggests that endogenous choline release from the prostate is largely from epithelial, rather than stromal tissue. 4. The possible involvement of facilitatory M(1) autoreceptors on cholinergic neurons in the effect of cholinomimetics was investigated. Tissue was incubated with (3)H-choline to label neuronal stores of acetylcholine and the subsequent release of (3)H-choline from the tissue was measured. Carbachol per se increased the release of (3)H-choline. 5. Transmural stimulation usually increased the release of (3)H-choline but in c. 30% of preparations there was a decrease. In the presence of carbachol there was a significant increase in the release of (3)H-choline during transmural stimulation of prostate lobes. However, there was no correlation between the two effects of carbachol; facilitating contractions produced by transmural stimulation and enhancing (3)H-choline release during transmural stimulation. The finding provides no evidence that facilitatory M(1) autoreceptors on cholinergic neurons play a major role in the facilitation of contractions.