This outstanding proposal plans to study and contrast the role of purinergic actions and cholinergic actions in the bladder. With evidence suggesting some gender specificity in purinergic functional significance, the project will also investigate mechanisms involved in sex hormone regulation of purinergic activity in the bladder. The majority of the work will be done in rats with some investigation performed on strips from human bladders. The methods to investigate these questions are in vivo cystometry in conscious, unrestrained rats, mRNA analysis of bladder tissue from rats, and ligand binding studies. In vivo studies include conscious animal studies to compare and contrast the relative importance of purinergic and cholinergic innervation of the bladder. In vitro whole bladder preparations for similar comparisons will complement the in vivo studies. In vitro studies of receptor subtypes using specific agonists, ecto-ATPase antagonists, and mRNA and ligand binding studies will provide information about the presence of receptor subtypes and the mechanisms involved in gender differences in purinergic responsiveness in the bladder. Calcium studies will be performed to determine the involvement of calcium in purinergic responses. Lastly, in vitro studies of rat and human bladder strip contractility will be done to compare animals and human tissues in males and females to determine any gender specificity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK051384-04
Application #
6124809
Study Section
Special Emphasis Panel (ZRG4-GMB (05))
Program Officer
Mullins, Christopher V
Project Start
1996-12-22
Project End
2001-11-30
Budget Start
1999-12-15
Budget End
2001-11-30
Support Year
4
Fiscal Year
2000
Total Cost
$166,666
Indirect Cost
Name
Albany College of Pharmacy
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
797866969
City
Albany
State
NY
Country
United States
Zip Code
12208
Longhurst, Penelope (2004) Developmental aspects of bladder function. Scand J Urol Nephrol Suppl :11-9
Longhurst, Penelope A; Levendusky, Mark C; Bezuijen, Martina W (2004) Diabetes mellitus increases the rate of development of decompensation in rats with outlet obstruction. J Urol 171:933-7
Bezuijen, Martina W F; Levendusky, Mark C; Longhurst, Penelope A (2003) Functional response of bladder strips from streptozotocin diabetic rats depends on bladder mass. J Urol 169:2397-401
Longhurst, Penelope A (2003) Functional development of the rat urinary bladder after pre- or postpubertal castration. Pharmacology 67:72-82
Longhurst, Penelope A (2002) In vitro rat bladder function after neonatal estrogenization. J Urol 168:2695-9
Schroder, Annette; Uvelius, Bengt; Capello, Seth A et al. (2002) Regional differences in bladder enlargement and in vitro contractility after outlet obstruction in the rabbit. J Urol 168:1240-6
Moore, Courtenay K; Levendusky, Mark; Longhurst, Penelope A (2002) Relationship of mass of obstructed rat bladders and responsiveness to adrenergic stimulation. J Urol 168:1621-5
Longhurst, P A; Uvelius, B (2001) Pharmacological techniques for the in vitro study of the urinary bladder. J Pharmacol Toxicol Methods 45:91-108
Longhurst, P A; Levendusky, M (2000) Influence of gender and the oestrous cycle on in vitro contractile responses of the rat urinary bladder to cholinergic stimulation. Br J Pharmacol 131:177-84
Longhurst, P A; Levendusky, M (1999) Pharmacological characterization of beta-adrenoceptors mediating relaxation of the rat urinary bladder in vitro. Br J Pharmacol 127:1744-50