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Xun Zhang, Nan Wang, Alison Schroeder, Kristine A. Erickson; Expression of Adenylate Cyclase Subtypes II and IV in the Human Outflow Pathway. Invest. Ophthalmol. Vis. Sci. 2000;41(5):998-1005.
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purpose. It has been demonstrated that low doses of pilocarpine and
other muscarinics substantially increase outflow facility in the
isolated human outflow system devoid of ciliary muscle. These
cholinergic-induced facility responses were thought possibly to be due
to elevation of cAMP as a result of the presence of adenylate cyclases
II (AC-II) and IV (AC-IV). Therefore, whether these isoforms are
present in outflow tissues was examined.
methods. Human anterior segments were perfused with carbachol
(10−9–10−5 M), and outflow facility and cAMP
levels in the perfusate were measured simultaneously. Isolated
trabecular meshwork (TM) were incubated with carbachol
(10−7 M), and the subsequent changes in cAMP were measured
by radioimmunoassay. AC-II and AC-IV were characterized in ocular
tissue with reverse transcription–polymerase chain reaction and in
results. Outflow facility increased, in a dose–dependent manner, by 10%, 16%,
and 27% in response to 10−9, 10−7, and
10−5 M carbachol, respectively. Similarly, cAMP increased
by 9%, 70%, and 210% in response to 10−9,
10−7, and 10−5 M carbachol, respectively. In
addition, cAMP levels significantly increased by 39% in isolated TM
strips incubated with 10−7 M carbachol. AC-II was detected
in most normal tissue examined, but not in any cultured cell lines or
any glaucomatous tissue. AC-IV was also widely expressed in most normal
tissues, faintly detected in some glaucoma tissue, but not detected in
most cultured cells.
conclusions. The presence of AC-II and AC-IV in outflow tissues supports the
hypothesis that cholinergics may indeed exert an effect on outflow
facility, mediated by cAMP, which is independent of muscle
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