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.
Tian
B
B
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, USA.
Millar
C
C
Kaufman
P L
PL
Bershadsky
A
A
Becker
E
E
Geiger
B
B
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