Effects of vasoactive intestinal polypeptide (VIP) and cyclic AMP on isolated dilator pupillae muscle of albino rabbit eye.

The iris dilator muscle strips were dissected from the albino rabbit eye pretreated with 0.5% topical indomethacin and were incubated in a Krebs-Ringer solution. After pretreatment with 3 X 10(-5)M of L-phenylephrine, vasoactive intestinal polypeptide (VIP) was added to the incubation medium at final concentrations ranging from 1 X 10(-10) to 3 X 10(-7)M. The VIP effects on the tension of the dilator muscles and the cyclic AMP (c-AMP) levels in the muscles determined by a radioimmunoassay method were correlated. VIP induced a dose-dependent relaxation of the dilator muscles in the VIP concentration range between 3 X 10(-10) and 3 X 10(-8)M: the ED50 obtained from 21 muscle strips averaged 6.08 +/- 1.34 (mean +/- SEM) X 10(-9)M. The c-AMP level in the dilator muscles increased in a dose-dependent manner in the VIP concentration range from 1 X 10(-9) to 1 X 10(-7)M: the ED50 was computed to be 5.12 X 10(-9)M. The dose-response relationships both for the muscle tension and for the c-AMP level were similar. The time-courses in c-AMP change and muscle relaxation were compared. The c-AMP level increased significantly prior to the onset of muscle relaxation after VIP treatment (10(-7)M), and the level reached a maximum when the muscle relaxation was almost completed. It was concluded that the dilator muscle relaxation by VIP is mediated by an increase in the intracellular c-AMP.