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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nguyen, Dan-thanh T. Lam, Michelle Exintaris, Betty Lang, Richard J. |
| Description | Author Affiliation: Exintaris B ( Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia. exintaris@pharm.monash.edu.au) |
| Abstract | BACKGROUND AND PURPOSE: Changes in smooth muscle tone of the prostate gland are involved in aetiology of symptomatic prostatic hyperplasia, however the control mechanisms of prostatic smooth muscle are not well understood. Here, we have examined the role of internal Ca(2+) compartments in regulating slow wave activity in the guinea pig prostate. EXPERIMENTAL APPROACH: Standard intracellular membrane potential recording techniques were used. KEY RESULTS: The majority (89%) of impaled cells displayed 'slow wave' activity. Cyclopiazonic acid (10 micromol.L(-1)) transiently depolarized (3-9 mV) the membrane potential of the prostatic stroma and transiently increased slow wave frequency. Thereafter, slow wave frequency slowly decreased over 20-30 min. Ryanodine transiently increased slow wave frequency, although after 30 min exposure slow wave frequency and time course returned to near control values. Caffeine (1 mmol.L(-1)) reduced slow wave frequency, accompanied by membrane depolarization of about 8 mV. Blockade of inositol trisphosphate receptor (IP(3)R)-mediated Ca(2+) release with 2-aminoethoxy-diphenylborate (60 micromol.L(-1)) or Xestospongin C (3 micromol.L(-1)) or inhibiting phospholipase C and IP(3) formation using U73122 (5 micromol.L(-1)) or neomycin (1 and 4 mmol.L(-1)) reduced slow wave frequency, amplitude and duration. The mitochondrial uncouplers, p-trifluoromethoxy carbonyl cyanide phenyl hydrazone (1-10 micromol.L(-1)), carbonyl cyanide m-chlorophenylhydrazone (1-3 micromol.L(-1)) or rotenone (10 micromol.L(-1)), depolarized the membrane (8-10 mV) before abolishing electrical activity. CONCLUSION AND IMPLICATIONS: These results suggest that slow wave activity was dependent on the cyclical release of Ca(2+) from IP(3)-controlled internal stores and mitochondria. This implies that intracellular compartments were essential in the initiation and/or maintenance of the regenerative contractile activity in the guinea pig prostate gland. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 156 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2009-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Calcium Metabolism Inositol 1,4,5-Trisphosphate Receptors Physiology Mitochondria Myocytes, Smooth Muscle Prostate Animals Caffeine Pharmacology Calcium Channel Agonists Estrenes Guinea Pigs Intracellular Space Membrane Potentials Muscle Contraction Ultrastructure Neomycin Cytology Pyrrolidinones Ryanodine Ryanodine Receptor Calcium Release Channel Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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