Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiological mechanisms leading to endolymphatic hydrops in Meniere's disease are unknown. Changes in ionic permeability of the cellular membranes between the endolymph and the perilymph, which alter the composition and osmolarity of the inner ear fluid, may be a major factor in the etiology of endolymphatic hydrops. To determine the possible involvement of adenylate cyclase in the formation of endolymphatic hydrops, we measured the endolymphatic K+, Na+, Cl- activities (AK, ANa, ACl) and the endocochlear potential (EP) by means of ion-selective microelectrodes while inner ear adenylate cyclase was activated by perilymphatic perfusion with forskolin. We observed a large ACl increase accompanied by an EP increase during forskolin (2 x 10(-4) M) perfusion and a delayed AK decrease after perfusion. No measurable ANa change was observed. These results suggest that adenylate cyclase may regulate Cl- permeability of the endolymph-perilymph barrier and that adenylate cyclase plays a critical role in acute endolymphatic hydrops in Meniere's disease by altering the osmolarity of the endolymph.
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PMID:Adenylate cyclase modulation of ion permeability in the guinea pig cochlea: a possible mechanism for the formation of endolymphatic hydrops. 144 13

There are indications that endolymph homeostasis is controlled by intracellular cAMP levels in cells surrounding the scala media. Cholera toxin is a potent stimulator of adenylate cyclase, i.e. it increases cAMP levels. We hypothesized that perilymphatic perfusion of cholera toxin might increase endolymph volume by stimulating adenylate cyclase activity, providing us with a pharmacological model of acute endolymphatic hydrops (EH). Guinea pig cochleas were perfused with artificial perilymph (15 min), with or without cholera toxin (10 microg/ml). The endocochlear potential (EP) was measured during and after perfusion. The summating potential (SP), evoked by 2, 4 and 8 kHz tone bursts, was measured via an apically placed electrode 0, 1, 2, 3 and 4 h after perfusion. Thereafter, the cochleas were fixed to enable measurement of the length of Reissner's membrane, reflecting EH. After perfusion the EP increased significantly over time in the cholera toxin group as compared to the controls. Also, the SP increased gradually at all frequencies in the cholera toxin group. Comparison within animals showed that the increase in SP became significant after 2 h at 4 kHz, after 3 h at 2 kHz and after 4 h at 8 kHz. In the control group the SP did not change significantly. The compound action potential (CAP) amplitude decreased monotonically over time at all frequencies in both the cholera toxin group and the control group, but it decreased faster in the cholera toxin group. Also, the cochlear microphonics amplitude decreased over time at all frequencies in both groups, but the decrease was significant only in the cholera toxin group after 3 h at 2 and 4 kHz. Quantification of the length of Reissner's membrane showed a small but insignificant enlargement in the cholera toxin treated animals compared to controls. These results are in accord with our view that EH is accompanied by an increase in SP and a decrease in CAP. Our results partially confirm previous results of Feldman and Brusilow (Proc. Natl. Acad. Sci. USA (1973) 73, 1761-1764). New aspects in relation to that study are the significantly increased EP and SP. In the classical EH model, based on obstruction of the absorptive function of the endolymphatic sac, increased SPs are accompanied by decreased EPs. In this cholera toxin model of EH, it is unlikely that the endolymphatic sac is involved. Apparently, EH can be based on mechanisms located in the cochlea itself as opposed to mechanisms located in the endolymphatic sac.
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PMID:Signs of endolymphatic hydrops after perilymphatic perfusion of the guinea pig cochlea with cholera toxin; a pharmacological model of acute endolymphatic hydrops. 1054 38