Effects of H-7 on the iris and ciliary muscle in monkeys.
OBJECTIVE
To determine the effects of H-7 on (1) iris and ciliary muscles (CMs) in living monkeys; (2) isolated monkey CM strips; (3) actomyosin contractility in cultured Swiss 3T3 cells.


METHODS
(1) Pupillary diameter (calipers) and accommodation (refractometer) in living monkeys were measured after topical, intracameral, or intravitreal administration of H-7 followed by systemic pilocarpine hydrochloride. (2) Pilocarpine-induced contraction of isolated monkey CM strips following administration of H-7 was measured in a perfusion chamber. (3) Actomyosin contractility in Swiss 3T3 cells cultured on thin silicone rubber film was determined by measuring cell-induced film wrinkles before and after administration of H-7.


RESULTS
Topical H-7 prevented anesthesia-induced miosis but did not affect resting refraction. Intracameral or intravitreal H-7 dilated the pupil and inhibited miotic but not accommodative responses to pilocarpine. H-7 inhibited pilocarpine-induced contraction of isolated monkey CM strips and reduced Swiss 3T3 cell contraction.


CONCLUSIONS
H-7 inhibits actin-based contractility in non-muscle cells and in monkey iris sphincter and CM. Under our in vivo experimental conditions, the effect on the iris predominates over that on the CM.
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, USA.
B
B
Tian
C
C
Millar
P L
PL
Kaufman
A
A
Bershadsky
E
E
Becker
B
B
Geiger
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000065:Accommodation, Ocular / Q000187:drug effects; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002924:Ciliary Body / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007498:Iris / Q000187:drug effects*; D008252:Macaca fascicularis; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009883:Ophthalmic Solutions; D010862:Pilocarpine / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011680:Pupil / Q000187:drug effects; D012029:Refraction, Ocular / Q000187:drug effects
D004791:Enzyme Inhibitors; D009883:Ophthalmic Solutions; D047428:Protein Kinase Inhibitors; D010862:Pilocarpine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000205:Actomyosin