dinoprost and apraclonidine

Single cells were prepared from guinea pig tracheal smooth muscle and used in an experiment on the contraction mechanisms for norepinephrine and a study on the change of alpha 2-adrenoceptors with age. Specific bindings of [3H]p-aminoclonidine to the single cells from the tracheal smooth muscles of 6- and 40-week-old guinea pigs were saturable and analyzed by Scatchard plot. The maximum number of [3H]p-aminoclonidine binding sites was larger in the preparation from 40-week-old guinea pigs than that from 6-week-old animals, while its dissociation constant did not change with age. The amount of prostaglandin F2 alpha released from the single cells was increased by norepinephrine, not affected by phenylephrine, and reduced by an alpha 2-antagonist such as yohimbine. The amount released by norepinephrine was significantly larger in the preparation from 6-week-old guinea pigs than that from 40-week-old animals. These results suggest that the age-related decrease in the potency of norepinephrine is due to reduction in the amount of excitable prostaglandin F2 alpha released by the drug, but not to a change in the total amount of alpha 2-adrenoceptors or the dissociation constant of the drug with respect to these adrenoceptors. Furthermore, alpha 2-adrenoceptors in the tracheal smooth muscle cell play an important role in the release of prostaglandin F2 alpha and the production of contractile responses of these muscles.

Topics: Age Factors; Animals; Cells, Cultured; Clonidine; Dinoprost; Guinea Pigs; Male; Muscle, Smooth; Norepinephrine; Trachea; Tritium

The effects of aging on alpha 2-adrenoceptor mechanisms in tracheal preparations isolated from 3-, 6-, 10-, 40- and 100-week-old guinea-pigs were studied. The potency of noradrenaline decreased with age. The specific binding of [3H]p-aminoclonidine to microsomal fractions prepared from tracheal smooth muscles from 6- and 40-week-old guinea-pigs was analysed by Scatchard analysis. The capacity of maximum binding sites of [3H]p-aminoclonidine was greater in the preparations from 40-week-old guinea-pigs than in 6-week-old animals, whereas the dissociation constant did not change with age. The amount of prostaglandin F2 alpha released by noradrenaline and the contractile response to prostaglandin F2 alpha decreased with age. These results suggest that an age-related decrease in the potency of noradrenaline is due to the decrease in the amount of excitable prostaglandin F2 alpha released by noradrenaline and in the contractile response to prostaglandin F2 alpha, but not to a change in the total number of alpha 2-adrenoceptors or in the dissociation constant of a drug from alpha 2-adrenoceptors. Extraneuronal uptake also plays a role in the response to noradrenaline in the tracheal preparations from older guinea-pigs.

Topics: Adrenergic alpha-Agonists; Aging; Animals; Clonidine; Corticosterone; Dinoprost; Guinea Pigs; In Vitro Techniques; Kinetics; Male; Microsomes; Muscle Contraction; Muscle, Smooth; Norepinephrine; Prostaglandin D2; Receptors, Adrenergic, alpha; Trachea

Topics: Administration, Topical; Animals; Aqueous Humor; Clonidine; Dinoprost; Dinoprostone; Disease Models, Animal; Female; Flurbiprofen; Glaucoma; Intraocular Pressure; Laser Therapy; Macaca fascicularis; Pupil