Activating effect of ATP on NO/cGMP pathway in guinea pig cochlea / 生理学报

ABSTRACT

The present investigation was to study the relationship between ATP and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. Forty healthy purebred albino guinea pigs with sensitive pryer's reflex were randomly divided into five groups. Their cochleae were dissected and perfused immediately with different solutions. For the control group, the cochleae (group 1) were perfused with artificial perilymph basal solution (APBS, containing 100 micromol/L dipyridamole, 100 micromol/L L-Arg and 1 mmol/L IBMX). Other groups were respectively perfused group 2 with 330 micromol/L ATP, group 3 with 100 micromol/L L-NNA+330 micromol/L ATP, group 4 with 10 micromol/L ODQ+330 micromol/L ATP and group 5 with 10 micromol/L A-23187. All these reagents were freshly dissolved in artificial perilymph basal solution (APBS). The cochlear tissue specimens were collected and the average cGMP content was measured with (125)I-cGMP RIA kit. The results showed that there was no significant difference in the average cochlear tissue weights among different groups. The concentration of cGMP in the cochlear tissue of the groups perfused with ATP (59.541+/-8.744 fmol/mg) and A-23187 (55.416+/-7.018 fmol/mg) was significantly higher than those of the control group (30.089+/-4.876 fmol/mg), the groups perfused with L-NNA+ATP (28.761+/-5.019 fmol/mg) and ODQ+ATP (34.209+/-13.658 fmol/mg). No significant difference was observed between the group perfused with ATP and the one with A-23187, as well as among the control group and the groups perfused respectively with L-NNA+ATP and ODQ+ATP. These results suggest that ATP elevated the concentration of cGMP in cochlear tissue while administration of nonselective nitric oxide synthase inhibitor L-NNA and soluble guanylate cyclase inhibitor ODQ could prevent the increase of cGMP concentration induced by ATP. It is indicated that ATP is involved in the activation of NO/cGMP pathway by elevating concentration in the cytoplasm of the cochlea. In turn, NO/cGMP pathway may exert a negative action on the effects of ATP. It is suggested that there is an ATP/Ca(2+)-NO/cGMP pathway in the guinea pig cochlea. ATP and NO/cGMP pathway jointly regulate the function of the cochlea.