Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

Urological Research
M GoepelMartin C Michel

Abstract

The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and female pigs and in humans (Kd = 35 +/- 8 pM, Bmax = 153 +/- 30 fmol/mg protein). Atropine and subtype-selective antagonists had steep and monophasic competition curves in porcine and human detrusor with a rank order of potency of atropine > hexahydro-sila-difenidol > or = AF-DX 116 > or = pirenzepine, indicating the presence of a homogeneous population of M2 muscarinic receptors. In female pigs bladder outflow obstruction generated by partial urethral ligation or its surgical treatment by ileum augmentation or autoaugmentation did not significantly alter expression of muscarinic receptors or of alpha2A-adrenoceptors, but the power was insufficient to exclude alterations of less than 60%. We conclude that porcine and human detrusor express muscarinic receptors of the M2 subtype; despite these qualitative similarities the use of the porcine model may be limited by large biological variance with regard to quantitative receptor expression.

Citations

Aug 2, 2005·Naunyn-Schmiedeberg's Archives of Pharmacology·Tim SchneiderMartin C Michel
Jun 13, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Martin C Michel, Sergio Parra
Nov 23, 2000·British Journal of Pharmacology·T YamanishiR Chess-Williams
Jun 28, 2002·British Journal of Pharmacology·Charlotte FetscherMartin C Michel
Feb 24, 2001·Journal of Autonomic Pharmacology·D J SellersR Chess-Williams
Jul 19, 2002·Journal of Autonomic Pharmacology·R Chess-WilliamsD J Sellers
Nov 28, 2002·Autonomic & Autacoid Pharmacology·R Chess-Williams
Jan 31, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Michel A PontariMichael R Ruggieri
Dec 28, 2007·European Urology·Lambertus P W WitteMartin C Michel
May 1, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nicola ArrighiSandra Sigala
Jan 29, 2008·Pharmacology & Therapeutics·Martin C Michel, Maurits M Barendrecht
Jan 4, 2007·Autonomic & Autacoid Pharmacology·M M BarendrechtR M Levin
Oct 5, 2012·Acta Physiologica·P OchodnickyM C Michel
Nov 12, 2003·Biochemical Pharmacology·Matthias B StopeMartin C Michel
Oct 12, 2005·The Journal of Urology·Michael R RuggieriMichel A Pontari
Feb 14, 2008·Journal of Pharmacological Sciences·Abu Syed Md AnisuzzamanIkunobu Muramatsu
Sep 21, 2002·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Martin C Michel
Oct 9, 2003·The Journal of Pharmacology and Experimental Therapeutics·Tim SchneiderMartin C Michel
Feb 11, 2004·The Journal of Pharmacology and Experimental Therapeutics·Tim SchneiderMartin C Michel
Aug 10, 2000·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·A L DalmoseM M Swindle

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