Neutering alters the functional proportions of muscarinic receptor subtypes of the canine bladder

Fiona J. Dowell1, Victoria A. Coit2, Ian Gibson1, Neil P. Evans1. 1Division of Cell Sciences, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, United Kingdom, 2R(D)SVS, Division of Veterinary Clinical Sciences, The University of Edinburgh, Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, Midlothian, EH25 9RG, United Kingdom.

M3 receptors are the principle receptor subtype responsible for mediating bladder contraction in healthy canines (Choppin and Eglen, 2001). However, the proportions of muscarinic receptor subtypes within the urinary bladder may be altered in conditions such as acquired urinary incontinence, which commonly develops in neutered bitches. We have previously shown that carbachol mediated contraction of isolated bladder strips is significantly reduced in neutered compared to entire canines (Coit et al., 2008). This study investigated whether neutering altered the functional proportions of muscarinic receptor subtypes of the canine bladder.

Strips of detrusor were dissected from entire and neutered male and female canines euthanased by overdose of pentobarbital (200 mg kg-1) with informed owner consent. Cumulative concentration response curves were constructed to carbachol (1nM-0.1mM) in the presence or absence of subtype-selective antimuscarinics methoctramine (M2) and 4-DAMP (M3). Schild analysis was used to determine pKB values.

Figure 1. pKB values for bladder strips from (a) entire (n=9) and (b) neutered (n=8) canines. Shaded areas represent reported affinity ranges of methoctramine and 4-DAMP for the M2 (vertical stripes) and M3 (horizontal stripes) receptor subtypes.

white circle Female, white square Male.

These data confirm that contraction of detrusor in entire animals is mediated predominantly by the M3 receptor, but in neutered canines the M2 rather than the M3 receptor subtype appears dominant.

Choppin, A. & Eglen, R.M. (2001). Br J Pharmacol 132: 835-842.
Coit, V.A. et al. (2008). Eur. J. Pharmacol 584: 153-158.