The urinary bladder is a smooth muscle organ whose function is to collect and store urine (at low intravesical pressures); and then to periodically expel the urine via a highly coordinated sustained contraction. Similar to other smooth muscle organs, the contractile function of the bladder is mediated by energy generated via the metabolism of intracellular substrates and the efficient generation of metabolic energy. Any pathological process which interferes with intracellular substrate utilization and energy production would be expected to result in the serious impairment of bladder function. The proposed studies can be separated into three major areas: 1) Detailed studies on the relationship between intracellular energetics, metabolism and contraction in the normal bladder. These studies include a detailed analysis of the role of mitochondria in bladder metabolism and contractile function. 2) The effect of specific experimental pathologies (partial outlets obstruction, acute over distension, and supravesical diversion) on bladder biochemistry, metabolism, and how they relate to alterations in contraction and function. 3) Correlation of the biochemical and functional effects of the specific experimental pathologies with morphology, obtained through the detailed histological evaluation of both control and pathological models by light, fluorescence, and electron microscopy. Our long-range goal is to identify specific metabolic defects that can either cause specific bladder pathologies, or result from specific pathologies. The proposed studies are designed to generate specific new information on the relationship between bladder metabolism (energetics), bladder function, and bladder morphology. This information would be extremely valuable in increasing our understanding the biochemical, metabolic and functional changes that accompany the development of specific bladder pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK033559-04
Application #
3231986
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-12-01
Project End
1990-11-30
Budget Start
1987-12-15
Budget End
1988-11-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Levin, Robert M; Hudson, Alan P (2004) The molecular genetic basis of mitochondrial malfunction in bladder tissue following outlet obstruction. J Urol 172:438-47
Nevel-McGarvey, C A; Rohrmann, D; Levin, R M et al. (1999) Mitochondrial and mitochondrial-related nuclear genetic function in rabbit urinary bladder following reversal of outlet obstruction. Mol Cell Biochem 197:161-72
Zhao, Y; Levin, S S; Wein, A J et al. (1997) Correlation of ischemia/reperfusion or partial outlet obstruction-induced spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder. Urology 49:293-300
Yu, H I; Wein, A J; Levin, R M (1997) Contractile responses and calcium mobilization induced by muscarinic agonists in the rat urinary bladder: effects of age. Gen Pharmacol 28:623-8
Levin, R M; Hypolite, J A; Broderick, G A (1997) Evidence for a role of intracellular-calcium release in nitric oxide-stimulated relaxation of the rabbit corpus cavernosum. J Androl 18:246-9
Soyupak, B; Wein, A J; Levin, R M et al. (1996) Effect of ischemia of the rabbit bladder on Ca-Mg-activated ATP-ase activity. Neurourol Urodyn 15:666-71
Kwon, H Y; Longhurst, P A; Parsons, K et al. (1996) Effects of glucose deprivation on the contractile response of the rabbit bladder to repetitive stimulation. Neurourol Urodyn 15:71-8
Levin, R M; Hypolite, J A; Haugaard, N et al. (1996) Comparative response of rabbit bladder smooth muscle and mucosa to anoxia. Neurourol Urodyn 15:79-84
Yu, H J; Wein, A J; Levin, R M (1996) Age-related differential susceptibility to calcium channel blocker and low calcium medium in rat detrusor muscle: response to field stimulation. Neurourol Urodyn 15:563-76
Chen, M W; Buttyan, R; Levin, R M (1996) Genetic and cellular response to unilateral ischemia of the rabbit urinary bladder. J Urol 155:732-7

Showing the most recent 10 out of 110 publications