Summary: | 碩士 === 中山醫學大學 === 醫學研究所 === 93 === The effects of immunosupressants, tacrolimus (FK 506) and Cyclosporine on the micturition reflex were examined in anesthetized rats. Both FK 506 (i.t., 100μM, 5ul) and Cyclosporine produced increase in voiding threshold (VT, 178.14±20.19% and 151.93±18.86%, respectively, p<0.05, n=9) and holding duration (HD, 341.28±28.28% and 326.84±23.98%, respectively, p<0.05, n=9) and voiding volume (VV, 145.66±7.40% and 145.06±7.26%, respectively, p< 0.05, n=9). Pretreatment of glutamate (i.t., 100μM, 5 ul ; VT=102.39±2.82% and 104.94±3.89%, HD= 100.58 ± 6.37 % and 90.59±7.54%, VV=96.66±8.28% and 102.26±10.62%, p<0.05, n=9), and N-methyl-D-aspartic acid (NMDA, i.t., 100μM, 5 ul; VT= 101.07±2.08% and 103.15±4.43%, HD=104.35±8.04% and 87.96±8.55%, VV=92.20±5.08% and 94.86±10.49% in FK 506 and Cyclosporine, respectively, p<0.05, n=9), ameliorate the effect on voiding reflex elicited by intrathecal FK 506 and Cyclosporine. In addition, APV (i.t., 100μM, 1-5μl ) pretreatment exaggerated the effects elicited by FK 506 (HD= 698.78±98.34 % , VV=266.66±31.06%, p< 0.05, n=9), while no significant effect was elicited by NBQX pretreatment. On the contrary, NBQX (i.t., 20μM, 1-5μl) pretreatment exaggerated the effects elicited by Cyclosporine (HD=737.98±94.55% , VV=274.33±14.30%, p< 0.05, n=9), while no significant effect was elicited by APV pretreatment. indicating a glutamatergic neurotransmission was affected by FK 506. All these results demonstrate that FK 506 and Cyclosporine may induce a distinct modulation in bladder functions mediated by their effects on glutamatergic transmission.
Key words: FK 506,Cyclosporine, glutamate, NMDA, voiding reflex, urinary bladder
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