Detrusor responses to prostaglandin E2 and bladder outlet obstruction in wild-type and Ep1 receptor knockout mice.
OBJECTIVE
Prostaglandins (PGs) are suggested to be involved in the pathophysiology of different bladder disorders and it has been demonstrated that cyclooxygenase-2 expression is increased as a consequence of bladder outflow obstruction. We investigated whether the PGE2 receptor EP1 is involved in the regulation of normal micturition, the response to intravesical PGE2 administration, and the development of bladder hypertrophy and overactivity due to bladder outlet obstruction (BOO).


METHODS
Moderate BOO was created in EP1 receptor knockout (EP1KO) mice and their WT counterparts. After 1 week cystometry was performed in conscious animals before and after PGE2 instillation. Findings were compared to those in unobstructed control animals. Bladder wet weight was measured to document the degree of hypertrophy after BOO.


RESULTS
There was no difference between unobstructed EP1KO and WT mice in urodynamic parameters but EP1KO mice did not respond to intravesical PGE2 instillation, while WT mice showed detrusor overactivity. The lack of EP1 receptor did not prevent bladder hypertrophy due to BOO. After BOO WT mice had pronounced detrusor overactivity, while this was negligible in EP1KO mice.


CONCLUSIONS
The EP1 receptor appears not to be essential for normal micturition or the mediation of bladder hypertrophy due to BOO but it seems to have a role in the development of detrusor overactivity caused by PGE2 and outlet obstruction.
Department of Clinical Pharmacology, Lund University Hospital, 221 85 Lund, Sweden.
Annette
A
Schröder
Donald
D
Newgreen
Karl-Erik
KE
Andersson
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009929:Organ Size; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001748:Urinary Bladder Neck Obstruction / Q000473:pathology / Q000503:physiopathology*; D014554:Urination / Q000502:physiology; D014563:Urodynamics
C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone