Urol Res (1997) 25:19%206 © Springer-Verlag 1997
M. Goepel-A. Wittmann-H. Riibben. M.C. Michel
Comparison of adrenoceptor subtype expression
in porcine and human bladder and prostate
Received: 31 July 1996/Accepted: 16 October 1996
Abstract We have quantified and characterized 0tl- , ~2-
and 13-adrenoceptor subtypes in porcine bladder de-
trusor and bladder neck, human bladder detrusor, and
porcine and human prostate. ~1-, a2- and 13-ad-
renoceptor were identified in radioligand binding studies
using [3H]prazosin, [3H]RX 821002 and [125I]io-
docyanopindolol, respectively, as the radioligands. In
porcine male and female detrusor and bladder neck and
male prostate, adrenoceptors were detected in the order
of abundance 13 > ~2 >> ~1 (not detectable), with no
major differences between the sexes or between detrusor
and bladder neck. In human detrusor and prostate the
order of abundance was 13 > ~2 )) 0~1 (not detectable)
and 13>> ~1 > ~2, respectively. The ~2-adrenoceptors in
all tissues were homogeneously of the ~2A-Subtype as
evidenced by competition binding studies with
yohimbine, prazosin, ARC 239 and oxymetazoline. The
13-adrenoceptors represented a mixed population with a
dominance of the 13z-subtype in all tissues as demon-
strated by competition binding with ICI 118,551 and
CGP 20,712A. We conclude that pigs may be a suitable
model for studies of detrusor function with respect to
adrenoceptor expression. They may be less suitable for
studies of bladder neck or prostate function.
Key words Pig - Human • a2-Adrenoceptor -
13-Adrenoceptor • Bladder. Prostate
Introduction
Urinary incontinence and other forms of disturbed mi-
cturition are a major cause of morbidity which may gain
even greater importance with the growing portion of the
elderly in the population [20]. Normal bladder function
M. Goepel ([~). H. Riibben
Department of Urology, University of Essen Medical School,
Hufelandstr. 55, D-45t22 Essen, Germany
A. Wittmann. M.C. Michel
Department of Medicine, University of Essen, Essen, Germany
depends on a coordinated balance between pressure
developed by the detrusor muscle and resistance devel-
oped by the bladder neck, the urethra and, in males, the
prostate. In the filling phase relaxation of the detrusor
and contraction of the sphincters are required, while in
the micturition phase contraction of the detrusor and
relaxation of the sphincters are necessary. This is coor-
dinated by the integration of excitatory, inhibitory and
sensory nerves in control centers in the spinal cord and
brain [7]. While contraction of the detrusor muscle is
mainly controlled by cholinergic mechanisms [1], sym-
pathetic pathways may also contribute to the regulation
of detrusor tone and possibly even more importantly
may be involved in the control of resistance of the lower
urinary tract [1].
The sympathetic nervous system acts on three classes
of receptors (~, ~2 and 13) with at least three subtypes
each which are designated ala, alB, C*1I~, aaA, aZC, 131,132
and 133 [3, 10]. At the neuroeffector junction between
sympathetic nerves and smooth muscle cells, ~1- and ~2-
adrenoceptors generally mediate enhancements of con-
traction, while 13-adrenoceptors mostly mediate smooth
muscle relaxation; prejunctional c,2-adrenoceptors may
additionally attenuate smooth muscle contraction by
inhibiting the release of contraction-causing neuro-
transmitters. Such observations have also been made in
smooth muscle of urogenital tissues [1]. While recent
research has accumulated large amounts of information
regarding expression of al-adrenoceptor subtypes in the
human prostate [12, 17, 22], only limited information is
available on subtypes of other adrenoceptors in the
prostate and on subtypes of all types of adrenoceptors in
the bladder.
Advances in physiological and pathophysiological
knowledge on micturition will require the use of adequate
animal models. An optimal animal model should not only
be large enough to allow detailed urodynamic measure-
ments and have sufficient anatomical similarity with hu-
mans but should also exhibit a similar profile of receptor
subtype expression. Therefore, we have compared ex-
pression of subtypes of ~1-, ~2- and [3-adrenoceptors in