Characterization of muscarinic cholinergic receptors in membrane preparations from rat prostatic adenocarcinoma

Abstract

The binding characteristics of 3H-quinuclidinyl benzilate (QNB) to muscarinic sites in isolated plasma membrane fractions from R-3327 Dunning tumors (H and AT-1 sublines); ventral, dorsolateral prostate; and urinary bladder of the rat were studied. QNB binding to all preparations, except from AT-1 tumors, was specific, saturable, and of high affinity. The AT-1 tumors completely lacked specific QNB binding. The muscarinic receptor density in H tumors was twofold and twentyfold higher than that in the ventral prostate and dorsolateral prostate respectively. The receptor density in the urinary bladder was approximately twofold higher than that in H tumors. The Kd values in H tumors and ventral prostate were very similar and significantly higher than that in dorsolateral prostate or the urinary bladder. QNB binding in H tumors was strongly inhibited by classical muscarinic receptor antagonists atropine and scopolamine, but poorly by the agonists carbacholine and pilocarpine. In contrast to scopolamine or atropine, inhibition by pirenzepine and AF-DX116 was relatively low. These data indicate that the muscarinic receptor in Dunning H tumors is of M3 type.

Muscarinic receptors and ligands in cancer

“…As shown in Table 1, muscarinic receptor expression is reported in tissues and cell lines derived from cancer of the brain (58) lung (114,115), ovary (93), pancreas (2,116), prostate (8,84), skin (15,16,108), stomach (76), and uterus (116). Nonetheless, because muscarinic receptor expression is common if not ubiquitous in all tissues, simply demonstrating expression of muscarinic receptors is insufficient to conclude that muscarinic signaling plays an important role in cancer progression.…”

“…In prostate adenomas, Lepor and Kuhar (79) initially described and Ruggieri et al (107) classified muscarinic receptors. Muscarinic receptors are expressed in both rat and human prostate cancer cell lines (8,84). In 1997, Rayford et al (104) reported that carbachol stimulates prostate cancer cell proliferation, an action attenuated by addition of muscarinic receptor inhibitors.…”

Age-related changes in the innervation of the prostate gland

“…With regard to parasympathetic cholinergic mechanisms, stimulation of muscarinic receptors of the M 3 subtype have been shown to stimulate proliferation of LNCaP prostate cancer cells as well as benign and cancerous primary prostate cells 135 . Similarly, in studies of the cancerous rat prostate, an increase in M 3 muscarinic receptor density was observed 136 . This suggests that M 3 muscarinic receptors may play a significant role in prostate cancer tumor growth and possibly also androgen-independent tumor progression.…”

Ionic and pharmacologic characteristics of epithelial cells in a semi‐intact preparation of the rat ventral prostate gland

“…Acetylcholine has previously been shown to have a strong hyperpolarizing influence in lacrimal [60] and parotid [61] gland cells, mainly through activation of K þ conductances. Muscarinic receptors (m3 subtype) have been localized both in the stroma and epithelia of the prostate gland [35] and are also expressed in rat prostate cancer cell lines [62]. Sympathetic cholinergic nerves exhibit an intimate spatial association with the glandular epithelium of the prostate [63] and muscarinic agonists directly stimulate cellular secretion in the gland [15].…”