Excitatory effects of bombesin receptors in urinary tract of normal and diabetic rats in vivo.
OBJECTIVE
Bombesin receptors (BB receptors) and bombesin related peptides are expressed in the lower urinary tract of rodents. Here we investigated whether in vivo activation of BB receptors can contract the urinary bladder and facilitate micturition in sham rats and in a diabetic rat model of voiding dysfunction.


METHODS
In vivo cystometry experiments were performed in adult female Sprague-Dawley rats under urethane anesthesia. Diabetes was induced by streptozotocin (STZ; 65mg/kg, i.p.) injection. Experiments were performed 9 and 20weeks post STZ-treatment. Drugs included neuromedin B (NMB; BB1 receptor preferring agonist), and gastrin-releasing peptide (GRP; BB2 receptor preferring agonist).


RESULTS
NMB and GRP (0.01-100μg/kg in sham rats; 0.1-300μg/kg in STZ-treated rats, i.v.) increased micturition frequency, bladder contraction amplitude and area under the curve dose dependently in both sham and STZ-treated rats. In addition, NMB (3, 10μg/kg i.v.) triggered voiding in >80% of STZ-treated rats when the bladder was filled to a sub-threshold voiding volume. NMB and GRP increased mean arterial pressure and heart rate at the highest doses, 100 and 300μg/kg.


CONCLUSIONS
Activation of bombesin receptors facilitated neurogenic bladder contractions in vivo. Single applications of agonists enhanced or triggered voiding in sham rats as well as in the STZ-treated rat model of diabetic voiding dysfunction. These results suggest that BB receptors may be targeted for drug development for conditions associated with poor detrusor contraction such as an underactive bladder condition.
Department of Pharmacology, Urogenix, Inc./Astellas Pharma, Durham, NC 27703, USA. Electronic address: aura240@yahoo.com.
F Aura
FA
Kullmann
Department of Pharmacology, Urogenix, Inc./Astellas Pharma, Durham, NC 27703, USA.
Grace I
GI
Wells
Department of Pharmacology, Urogenix, Inc./Astellas Pharma, Durham, NC 27703, USA.
David
D
McKenna
Department of Pharmacology, Urogenix, Inc./Astellas Pharma, Durham, NC 27703, USA.
Karl B
KB
Thor
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology; D009119:Muscle Contraction; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018004:Receptors, Bombesin / Q000819:agonists / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014554:Urination / Q000187:drug effects
D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B
Cystometry; Streptozotocin; Underactive bladder; Urethane anesthesia