Adenylyl and guanylyl cyclase activity in the choroid.
The choroid, a low-resistance vascular structure provides nourishment to and removal of potential toxic waste products from the adjacent non-vascularized outer layers of the retina, macula, and optic disc region and may be involved in the pathology of normal tension glaucoma. This study is aimed at delineating the biochemical pharmacology of vascular tone control in this tissue. By using a procedure to harvest fresh choroidal tissue, we studied some basic characteristics of the adenylyl (AC) and guanylyl cyclase (GC) enzyme systems in this tissue using the 3H-cAMP/32P-ATP tracer method. Compared to respective baseline measurements (100+/-SEM%), AC activity was stimulated (p < 0.05) by forskolin (FSK, 477+/-59%), fluoroaluminate (AlF(4), 360+/-10.3%), isoproterenol (ISO, 129+/-5.5%), vasoactive intestinal peptide (VIP, 132+/-6.1%), calmodulin (CAM)+Mn2+ (196+/-69%), and dose-dependently by prostaglandin (PG) E2 (up to 162+/-3.6%). The antagonist drug calmidazolium inhibited the CAM-dependent increase but also blocked basal activity (47+/-2.0%) without affecting the FSK response. Other CAM blockers (TFP, W5) produced similar results but were not completely selective for CAM-activated cyclase. GDPbetaS, a blocker of G-protein coupling to AC did not affect AC responses to FSK, ISO, and AlF4, but decreased the response to PGE2. N-ethyl-carboxamido adenosine (NECA), which activates adenosine A2 receptors, did not synergize with FSK or add to ISO responses and did not activate AC by itself. In the GC system activity was stimulated (p< 0.05) by CAM+Mn2+ (239+/-27%), by atrial natriuretic peptide (ANP, up to 143+/-1.4%) and sodium nitroprusside (SNP, up to 179+/-1.6%). These results show that choroidal tissue has significant activities of the adenylyl and guanylyl cyclase second messenger systems potentially responsive to hormones/neurotransmitters that may control the degree of relaxation in this vascular tissue.
Schmidt
Karl-Georg
KG
Department of Ophthalmology and Pharmacology, Mount Sinai School of Medicine, New York, NY, USA. k.g.schmidt@gmx.de
Geyer
Orna
O
Mittag
T W
TW
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002829:Choroid / Q000187:drug effects / Q000201:enzymology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology
D006728:Hormones; D018377:Neurotransmitter Agents; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D015232:Dinoprostone