Interaction of vanadate and iodate oxyanions with adenylyl cyclase of ciliary processes.
Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated response of FSK in the presence of VO3- was due to an increase in Vmax without a change in the apparent affinity of FSK or VO3-, and therefore differs from the potentiated response of activated G-protein (Gs) and FSK, where the affinity of FSK was increased by 1-2 orders of magnitude. Potentiation occurred at low Mg2+ and was not observed at free [Mg2+] > 3 mM. Iodate (IO3-) inhibited the FSK, ISO, and VO3- activations of AC in ciliary process membranes (IC50, 0.3 mM). In vivo topical treatment of the rabbit eye with 50 microL of 5% NaIO3 had no effect alone but completely blocked the intraocular pressure response to a 50-microL topical dose of 1% FSK and partially blocked the response to a 50-microL dose of 0.001% ISO. These findings indicate that some AC enzymes may have a binding site for oxyanions which can directly regulate enzyme activity.
Mittag
T W
TW
Department of Ophthalmology, Mount Sinai School of Medicine, CUNY, New York 10029.
Guo
W B
WB
Taniguchi
T
T
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002924:Ciliary Body / Q000187:drug effects / Q000201:enzymology*; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007452:Iodates / Q000378:metabolism* / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D011817:Rabbits; D014638:Vanadates / Q000378:metabolism* / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D007452:Iodates; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D014638:Vanadates; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium; D007545:Isoproterenol