Evidence for Purinergic Neurotransmission in Human Urinary Bladder Affected by Interstitial Cystitis

Abstract

Detrusor specimens were obtained from 5 patients affected by interstitial cystitis (IC) and 5 patients with bladder carcinoma (controls). Muscle strips were prepared for in vitro pharmacological studies. In all detrusor strips taken from IC patients, an important portion of the electrically-induced contraction was atropine-resistant. In contrast, atropine-resistance was never observed in control detrusors. H1 and H2 antagonists did not affect noncholinergic contractile response which, conversely, was abolished following desensitization to alpha, beta methylene ATP (APCPP). Detrusor muscle from patients affected by IC exhibited an increase in sensitivity to APCPP and a decrease in sensitivity to acetylcholine with respect to control detrusor. Taken together these results are consistent with the presence of a purinergic neurotransmission in parasympathetic nerve terminals of the urinary bladder affected by IC, probably as a consequence of alterations in the innervation and/or electrical coupling between smooth muscle cells. The sensitivity of IC detrusor muscle to histamine was much lower than that of control detrusor, suggesting a desensitization of histamine receptors present in the bladder wall of IC patients.

The physiological function of lower urinary tract smooth muscle

“…Of interest however, is that with detrusor samples from human bladders displaying pathogical contractile overactivity, atropine-resistance emerges, with the residual contraction blocked by ABMA (Sjögren et al, 1982;Palea et al, 1993;Bayliss et al, 1999). One hypothesis for the emergence of ATP as a functional transmitter in human bladder pathologies is that ATP is released along with acetylcholine from parasymapthetic nerve varicosities.…”

Neural Control of the Lower Urinary Tract

“…Purinergic transmission has an important excitatory role in animal bladders but is not important in the normal human bladder. However, it appears to be involved in bladders from patients with pathological conditions such as detrusor overactivity (DO), chronic urethral outlet obstruction, or interstitial cystitis (87,494).…”

P2X receptor expression in mouse urinary bladder and the requirement of P2X1 receptors for functional P2X receptor responses in the mouse urinary bladder smooth muscle

“…In vitro and in vivo studies on rodents have shown the P2X receptor response can account for a considerable component (up to 50%) of the neurogenic bladder contraction (Brading & Williams, 1990;Hegde et al, 1998;Igawa et al, 1993). P2X receptors are expressed on normal human bladder (Hoyle et al, 1989;Inoue & Brading, 1991) however they do not appear to contribute to the neurogenic response (Palea et al, 1993;Sibley, 1984). In contrast, a considerable component of the neurogenic contraction is mediated by P2X receptors in tissues from patients with bladder disorders, e.g.…”

“…In contrast, a considerable component of the neurogenic contraction is mediated by P2X receptors in tissues from patients with bladder disorders, e.g. carcinoma or intestitial cystitis (Hoyle et al, 1989;Luheshi & Zar, 1990;Palea et al, 1993;Sjogren et al, 1982) suggesting that P2X receptors may play a role in disease states.…”