Enhancement of rat bladder contraction by artificial sweeteners via increased extracellular Ca2+ influx.
BACKGROUND
Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfame K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips.


METHODS
Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS) in the absence and presence of atropine, and with alpha,beta methylene ATP, potassium, calcium and carbachol.


RESULTS
Sweeteners 10(-7) M to 10(-2) M enhanced the contractile response to 10 Hz EFS compared to control (p<0.01). The atropine-resistant response to EFS was marginally increased by acesulfame K 10(-6) M, aspartame 10(-7) M and sodium saccharin 10(-7) M. Acesulfame K 10(-6) M increased the maximum contractile response to alpha,beta methylene ATP by 35% (+/-9.6%) (p<0.05) and to KCl by 12% (+/-3.1%) (p<0.01). Sodium saccharin also increased the response to KCl by 37% (+/-15.2%) (p<0.05). These sweeteners shifted the calcium concentration-response curves to the left. Acesulfame K 10(-6) M increased the log EC(50) from -2.79 (+/-0.037) to -3.03 (+/-0.048, p<0.01) and sodium saccharin 10(-7) M from -2.74 (+/-0.03) to 2.86 (+/-0.031, p<0.05). The sweeteners had no significant effect on the contractile response to carbachol but they did increase the amplitude of spontaneous bladder contractions.


CONCLUSIONS
These results suggest that low concentrations of artificial sweeteners enhanced detrusor muscle contraction via modulation of L-type Ca(+2) channels.
Dasgupta
Jaydip
J
University of Leicester, Prolapse and Incontinence Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK.
Elliott
Ruth A
RA
Doshani
Angie
A
Tincello
Douglas G
DG
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001218:Aspartame / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012439:Saccharin / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology*; D013843:Thiazines / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D020746:Calcium Channels, L-Type; D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D013549:Sweetening Agents; D013843:Thiazines; D011189:Potassium Chloride; D001285:Atropine; D000255:Adenosine Triphosphate; D002217:Carbachol; D012439:Saccharin; C006362:acetosulfame; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D001218:Aspartame