title: Characterization of ciliary muscle relaxation induced by various agents in cats.
abstract: OBJECTIVE
  To understand the cellular mechanism underlying the relaxation of ciliary muscle, relaxation induced by prostaglandins (PGs) and some other agents was characterized in the cat.
  
  
  METHODS
  Tone of isolated ciliary muscle was measured by means of a force-displacement transducer. Adenylate cyclase activity was determined with membrane fraction of ciliary muscle by measuring the formation of cyclic adenosine monophosphate (cAMP).
  
  
  RESULTS
  The addition of various PGs and isoproterenol relaxed the ciliary muscle that had been precontracted with 3 x 10(-6) M carbachol. The relaxation was dose dependent, with an EC50 of 2 x 10(-7) M for PGE2. The rank order of potency by which PGs induced relaxation (PGE2 = E1 > D2 > F2 alpha > I2) was identical with that reported for EP type prostaglandin receptor-mediated responses except for PGD2, which was more potent than expected. Agents that increased cellular cAMP, such as forskolin and IBMX, also relaxed the precontracted muscle. Nitric oxide donors, such as sodium nitroprusside and S-nitroso-N-acetyl-DL-penicillamine (SNAP), also caused dose-dependent relaxation. PGs and isoproterenol, but not nitroprusside, stimulated adenylate cyclase. The rank order of potency by which PGs stimulate adenylate cyclase was similar to that observed for muscle relaxation, suggesting that cAMP is the cellular second messenger for the PG-induced muscle relaxation and thus that PG receptors of EP2 and DP type are involved.
  
  
  CONCLUSIONS
  Relaxation of cat ciliary muscle is mediated by two independent mechanisms: a cAMP-dependent one, which includes beta-adrenergic, EP2, and DP receptor-mediated responses, and a cAMP-independent one, which includes the nitric oxide-induced mechanism.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Goh
authors.forename: Y
authors.initials: Y
authors.lastname: Hotehama
authors.forename: H K
authors.initials: HK
authors.lastname: Mishima
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002415:Cats; D002924:Ciliary Body / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D011453:Prostaglandins; D009569:Nitric Oxide; D002217:Carbachol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases