EFFECTS OF POLYAMINE SYNTHESIS INHIBITION ON POLYAMINES, GROWTH AND MECHANICAL-PROPERTIES IN HYPERTROPHIC RAT URINARY-BLADDER

The polyamines putrescine, spermidine and spermine, are ubiquitous int racellular metabolites associated with growth and protein synthesis. I n this study effects of polyamine synthesis inhibition on bladder grow th, polyamine levels and mechanical properties were investigated in ra t urinary bladder subjected to partial outflow obstruction that causes bladder hypertrophy. The S-adenosyl methionine decarboxylase inhibito r CGP-48664 (5 and 20 mg kg(-1)) was administered alone or in combinat ion with the ornithine decarboxylase inhibitor DFMO (500 mg kg(-1)), s tarting one day before creation of partial outflow obstruction and the n daily for 7 days. The bladder muscle level of putrescine was increas ed 38 times and that of spermine reduced by 4 times while spermidine w as unchanged after treatment with CGP-48664 (20 mg kg(-1)). The increa se in putrescine was abolished in animals receiving CGP-48664 in combi nation with DFMO. Treatment with polyamine synthesis inhibitors could not prevent or reduce the hypertrophy of the bladder as judged by blad der wet weight and protein contents. The effects on polyamine quantiti es were not associated with changes in Ca2+-force relationship or in a gonist and electrically stimulated force. In summary, treatment of rat s with polyamine synthesis inhibitors resulted in changes in polyamine levels in the growing urinary bladder but did not affect growth or me chanical properties.