In this study, all the anti-glaucoma agents tested had apparent ocular hypotensive effects in mice. Our data suggest that the mouse may be a useful animal for the evaluation of the pharmacological effects of agents with various anti-glaucoma mechanisms, and for the evaluation of the enhanced ocular hypotensive effects that may be induced by the concomitant use of 2 anti-glaucoma agents.

Repeated topical administration of any of the three prostaglandin F(2alpha) analogs increased ONH blood flow in rabbits, without changing heart rate. The increase in ONH blood flow induced by tafluprost was greater than that induced by latanoprost (P = 0.086) or travoprost (P = 0.037) at 60 min on day 28.

TM-gel administered once-daily was as effective at lowering IOP as TM administrated twice-daily over the 12-week experimental period. This study reveals that, in rabbits, both formulations of the timolol maleate induced significant IOP reductions in the dark phase and decreased the amplitudes of the circadian fluctuations in IOP for 12 successive weeks.

A ubiq~ti~ATP-de~ndent proteinase complex (26 S proteasome) was highly pm%ied from rabbit skeletal muscle. The purified 26 S proteasome easily dissociated into a 20 S proteasome and a regulatory subunit complex on nondenat~ng PAGE. By using cleavable and non-cleavable cross-linkers, it was revealed that the 26 S proteasome exists in two isoforms: one (D complex) consists of the 20 S proteasome and the regulatory subunit complex in the ratio of one to two, while the other (C complex) exists in an equal molar ratio. Molecular masses of the former and the latter isoforms were estimated to be 1,700 kDa and 1,400 kDa, respectively, by gel filtration, and 2,400 kDa and 1,400 kDa, respectively, by Ferguson plot analysis. Furthermore, both isoforms efficiently hydrolyzed Sue-Leu-Leu-Val-Tyr-MCA and ubiquitin-conjugated ["'I]lysozyme. These results suggest that the D and C complexes are active proteinase complexes, most probably corresponding to the dumbbell-like and mushroom-like (or space joule-like) molecules, respectively.ATP-dependent; Ubiquitin; Protease; Proteasome; Muscle (rabbit) I~RODUCTI~NA ubiquitin(Ub)/ATP-dependent proteinase complex, 26 S proteasome, plays a key role in intracellular proteolysis of the abnormal and short-lived proteins (for review see [l-4]). In this pathway, substrate proteins are first poly-ubiquitinated by El (Ub activating enzyme), E2 (Ub carrier protein, Ub conjugating enzyme) and E3 (Ub ligase, N-recognin) in an ATP-dependent manner, and degraded by the 26 S proteasome in an ATP-dependent fashion again.An ATP-dependent 26 S protease, which has recently been called 26 S proteasome [1,2], was first purified from rabbit reticulocyte lysate by Hough et al. [5]. Their purified preparation gave two bands on non-denaturing PAGE, both of which had a Suc-Leu-Leu-Val-Tyr-MCA-hydrolyzing activity and appeared to comprise the 20 S proteasome and the higher molecular mass subunits (34-l 10 kDa), the latter of which is believed to be a regulatory subunit complex including ATPase sub-*Corresponding author. Fax: (81) (11) 717 3167. **Present address; Bioscience and Chemistry Division, Hokkaido National Industrial Research Institute, Toyohira-ku, Sapporo 062, Japan.Abbreviations: AMC, 7-amino-4methylcoumarin; DMA, dimethyladipimidate; DTT, ditbiothreitol; DTBP, dimethyl 3,3'dithiobispropionimidate;MCA, 4-methylcoumaryl-7-amide; PAGE, polyacrylamide gel electrophoresis; SDS, sodium dodecyi sulfate; Sue, succinyi; 2D, two-dim~sion~; Ub, ubiquitin.units [5,6]. ~though recent progress in their studies of the 26 S proteasome agrees with their previous findings concerning the presence of two isoforms in the 26 S proteasome [7], molecular entities of the two isoforms and the reason for the presence of two isofonns in a purified preparation of the 26 S proteasome remain unclear. Several ideas have been proposed concerning the constituent complexes of the 26 S proteasome: the rabbit reticulocyte 26 S complex seems to comprise three factors: CF-1 (600 kDa), CF-2 (250 kDa), and CF-3 (650 kDa) [8], among which C...

In vitro rabbit lacrimal gland protein secretion is comparable to that in vivo. Cholinergic-mediated control of rabbit lacrimal gland protein secretion occurs through stimulation of the M3 muscarinic receptor subtype.