Abstract
Introduction. We have previously shown that ATP is released from mucosal strips in response to stretch, capsaicin and acid; moreover, the mucosa is able to contract in response to neurokinin A (NKA) (Sadananda et al, 2008, 2009). Our ultrastructural studies have found myofibroblasts under the urothelial cells, and these appear to be innervated by nerves containing dense-cored peptidergic vesicles (Sandow et al, 2010). Aims. Here, we examined (1) whether mucosal strips were able to contract to agents other than NKA and carbachol; (2) their ability to respond to electrical field stimulation (EFS); and (3) whether NKA could evoke ATP release from the bladder mucosa. Methods. Porcine bladders were obtained on ice from an abattoir and dissected immediately on arrival. Smooth muscle-denuded mucosal strips were suspended in organ baths; contraction was elicited and ATP release was measured as described (Sadananda et al, 2008, 2009). Contractile data were expressed as percent of maximal carbachol response. Results. Bradykinin, histamine, 5HT and endothelin elicited concentration-dependent contractions of porcine mucosal strips, with EC50 values 0.66, 1.83, 0.55 and 0.18 µM, respectively. In preliminary experiments, EFS (0.1 msec, 70V) elicited moderate frequency-dependent contractile responses. However, responses were unaffected by 1µM atropine (P>0.05), 1µM tetrodotoxin (TTX), or the tachykinin NK2 receptor antagonist SR48968 (10nM). A low concentration of NKA (1 nM) had no effect on tone of the strips but caused a significantly higher ATP release compared with basal; desensitisation of ATP release was observed on repeat administration of NKA. Discussion. Porcine mucosal strips appear to express a number of different receptors. The comparatively slow contractile responses induced by EFS may be due to direct stimulation of contractile elements (such as myofibroblasts), rather than nerve-mediated. NKA-induced ATP release in the bladder mucosa suggests an important role for tachykinins in bladder sensation.