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Vol. 289, Issue 3, 1362-1369, June 1999
1 Recognition Sites in Rabbit Iris-Ciliary Body:
Topical 1-Site Agonists Lower Intraocular
Pressure1
Department of Pharmacology, University of Bologna, Bologna, Italy
In this study, we examined the presence of 
1 and
2 sites in the rabbit iris-ciliary body by receptor
binding and investigated their effects on intraocular pressure (IOP) in
albino rabbits. The iris-ciliary body has binding sites for the
1-site agonist [3H](+)-pentazocine
(Kd = 4.6 nM;
Bmax = 212 fmol/mg protein) and 2 sites labeled with
[3H]1,3-di-o-tolylguanidine (DTG)
(Kd = 8.2 nM;
Bmax = 1120 fmol/mg protein). In competition
binding studies, (+)-pentazocine and the antagonist NE-100
displayed high affinity for 1 sites
(Ki = 2.1 and 2.4 nM, respectively), whereas
(+)-N-allylnormetazocine (NANM) was less potent
(Ki = 178 nM). Unilateral topical
(+)-pentazocine (0.01-0.1%) caused a significant dose-related
reduction of IOP in ocular normotensive rabbits and in the
-chymotrypsin model of ocular hypertension. (+)-NANM was less potent
than (+)-pentazocine. Neither compound altered the IOP of the
contralateral eye, and their hypotensive activity was blocked by NE-100
that, by itself, had no effect on IOP. (
)-Pentazocine, ()-NANM, and
DTG had no effect on IOP. DTG prevented the hypotensive effect of
(+)-pentazocine, suggesting that it acts as a 1-site
antagonist. -Site ligands did not affect pupil diameter or cause
ocular inflammation. Topical [3H](+)-pentazocine reaches
the intraocular tissues within 30 min, and its uptake in the
iris-ciliary body and retina was significantly reduced by topical
pretreatment with NE-100, as expected for a receptor-specific agent.
Reverse-phase HPLC confirmed the presence of intact (+)-pentazocine in
iris-ciliary body homogenates. 1-Site agonists may offer
a novel class of agents potentially effective in the control of ocular hypertension.
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