King's College London

TY - JOUR

T1 - Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia

AU - Pritchard, Sara

AU - Jackson, Michael J.

AU - Hikima, Atsuko

AU - Lione, Lisa

AU - Benham, Christopher D.

AU - Chaudhuri, K. Ray

AU - Rose, Sarah

AU - Jenner, Peter

AU - Iravani, Mahmoud M.

PY - 2017/5/17

Y1 - 2017/5/17

N2 - Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively. Contractions by exogenous carbachol, histamine or ATP were similar and no differences in the magnitude of noradrenaline-induced relaxation were seen in detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix jacchus). However, the neurogenic contractions following electrical field stimulation of the intrinsic nerves (EFS) were markedly greater in strips obtained from MPTP treated animals. EFS evoked non-cholinergic contractions following atropine were also greater but the contribution of the cholinergic innervation as a proportion of the overall contraction was smaller in the detrusor strips of MPTP treated animals, suggesting a preferential enhancement of the non-cholinergic transmission. Although dopaminergic mechanism has been proposed to underlie bladder hyperreflexia in MPTP-treated animals with intact bladder, the present data indicates that the increased neurogenically mediated contractions where no extrinsic innervation exists might be due to long-term adaptive changes locally as a result of the loss of the nigrostriatal output.

AB - Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively. Contractions by exogenous carbachol, histamine or ATP were similar and no differences in the magnitude of noradrenaline-induced relaxation were seen in detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix jacchus). However, the neurogenic contractions following electrical field stimulation of the intrinsic nerves (EFS) were markedly greater in strips obtained from MPTP treated animals. EFS evoked non-cholinergic contractions following atropine were also greater but the contribution of the cholinergic innervation as a proportion of the overall contraction was smaller in the detrusor strips of MPTP treated animals, suggesting a preferential enhancement of the non-cholinergic transmission. Although dopaminergic mechanism has been proposed to underlie bladder hyperreflexia in MPTP-treated animals with intact bladder, the present data indicates that the increased neurogenically mediated contractions where no extrinsic innervation exists might be due to long-term adaptive changes locally as a result of the loss of the nigrostriatal output.

UR - http://www.scopus.com/inward/record.url?scp=85019879600&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0175797

DO - 10.1371/journal.pone.0175797

M3 - Article

AN - SCOPUS:85019879600

VL - 12

JO - PL o S One

JF - PL o S One

SN - 1932-6203

IS - 5

M1 - e0175797

ER -