Effect of the Bowman-Birk inhibitor (a soy protein) on in vitro bladder neck/urethral and penile corporal smooth muscle activity.
OBJECTIVE
The Bowman-Birk inhibitor (BBI), is a serine protease inhibitor derived from soy beans, which is presently being evaluated in clinical trials for its ability to serve as a cancer preventive or anti-inflammatory agent. The form of BBI currently in clinical trials is known as Bowman-Birk inhibitor concentrate (BBIC). There have been anecdotal reports from patients of improved voiding and sexual functions in the ongoing BBIC trials. The objective of this study was to quantify the effect of BBI and BBIC on urethral and corporal smooth muscle activity.


METHODS
In vitro muscle strip studies of New Zealand White rabbit urethra/bladder neck and penile corpora in the presence or absence of BBI or BBIC incubation (5 mg/mL) were performed.


RESULTS
In dose-response curves to alpha stimulation, BBI mediated a shift to the right (decreased receptor sensitivity in bladder/urethra as well as corpora with no change in the maximal response). Bladder base/ urethra contraction by field stimulation was significantly inhibited by BBI at higher frequencies (1-32 Hz) (12.2 + 0.8 g vs. 6.3 + 0.75 g, P < 0.05). BBI inhibited field stimulated relaxation of corporal muscle at lower frequencies. Muscarinic contraction of the bladder neck/urethra in alpha prestimulated tissue was significantly inhibited by BBI (5.3 + 0.2 g vs. 2.7 + 0.1 g, P < 0.05). BBI has an inhibitory effect on alpha adrenergic dose-response curves in bladder neck/urethral and corpora smooth muscle. BBI also significantly inhibited neurohumoral cholinergic release and in vitro muscarinic contraction of the urethra. The effects on corpora relaxation were less pronounced.


CONCLUSIONS
The data suggest that the phytochemical BBI may promote physiologic effects of urethral relaxation and improved voiding by unique mechanisms and deserves further study as a pharmacologic agent for lower urinary tract symptoms.
Malkowicz
S Bruce
SB
Division of Urology, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. malkowic@mail.med.upenn.edu
Liu
Shih-Ping
SP
Broderick
Gregory A
GA
Wein
Alan J
AJ
Kennedy
Ann R
AR
Levin
Robert M
RM
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009994:Osmolar Concentration; D010413:Penis / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000008:administration & dosage; D011817:Rabbits; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D018679:Cholinergic Agonists; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors; D010656:Phenylephrine; D002217:Carbachol