Cholinergic and purinergic responses in isolated human detrusor in relation to age.
OBJECTIVE
We investigated whether the contractility of isolated human detrusor muscle, responsiveness to commonly used spasmolytic drugs, and expression of selected muscarinic and purinergic (P2X) receptor subtypes (M2, M3, P2X1 and P2X3) change with age.


METHODS
Tissues were taken from 63 patients 37 to 84 years old undergoing radical cystectomy. Specimens from 49 patients were used for contractility studies and those from 50 were used for mRNA analysis.


RESULTS
Propiverine, oxybutynin, tolterodine and atropine decreased contractions evoked by electric field stimulation to different degrees. However, neither the efficacy nor potency of the drugs showed age related changes. Since human detrusor muscle shows atropine resistant noncholinergic responses, we also studied the putative age dependence of concentration-response curves to the muscarinic agonist carbachol, and the purinergic agonists adenosine triphosphate (ATP) and alpha-beta-methylene-ATP. Sensitivity to alpha-beta-methylene-ATP increased with age, while the efficacy and potency of spasmolytic drugs did not depend on age. In addition, mRNA detected for M2, M3, P2X1 and P2X3 receptors did not change with age.


CONCLUSIONS
Our results do not provide evidence for age related contractile deterioration in human detrusor muscle strips, nor do they suggest that responses to anticholinergic spasmolytic drugs change substantially with age.
Wuest
Melinda
M
Institute of Pharmacology and Toxicology, Dresden University of Technology, Department of Urology, University Hospital Carl-Gustav Carus, Dresden, Germany.
Morgenstern
Kathrin
K
Graf
Eva-Maria
EM
Braeter
Manfred
M
Hakenberg
Oliver W
OW
Wirth
Manfred P
MP
Ravens
Ursula
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009122:Muscle Hypertonia / Q000503:physiopathology*; D010276:Parasympatholytics / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000187:drug effects / Q000502:physiology; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000502:physiology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D058477:Receptors, Purinergic P2X3; D046509:Tissue Culture Techniques; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
C546407:P2RX3 protein, human; D010276:Parasympatholytics; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011950:Receptors, Cholinergic; D011983:Receptors, Purinergic; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3