The presence of serotonin (5-HT1) receptors negatively coupled to adenylate cyclase in rabbit and human iris-ciliary processes.
Serotonin (5-hydroxytryptamine, 5-HT) reduces forskolin-induced stimulation of cyclic AMP in rabbit iris-ciliary body (ICB) homogenates. The effect is dose dependent and can be mimicked by a number of 5-HT1 receptor agonists including 5-carboxamidotryptamine (5-CT) and RU 24969 [5-methoxy-3-(1,2,3,6, tetrahydro-4-pyridinyl)-1-indole]. The inhibitory effects of 5-CT and the 5-HT1A selective agent 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) on forskolin stimulated adenylate cyclase activity are greater in isolated ciliary processes than in the iris musculature. Spiperone and propranolol significantly antagonize the action of 5-CT in the iris-ciliary body, while ketanserin (5-HT2 antagonist) and ICS 205930 (5-HT3/4 blocker) were without influence, indicating the presence of the 5-HT1A subtype of receptor. Studies carried out on human ICB homogenates also suggest the presence of 5-HT1A-like receptors, although these receptors are not identical to those in rabbit. Similarities include dose-dependent decreases in cAMP levels stimulated by forskolin elicited by 1-(3-chlorophenyl) piperazine (mCPP), 5-CT and 8-OH-DPAT. Moreover, the inhibitory effect of 5-CT can also be significantly reduced by the 5-HT1 receptor antagonist, propranolol. However, unlike the case of rabbit tissue, spiperone was ineffective in abolishing the 5-CT response in human ICB homogenates.
Barnett
N L
NL
Nuffield Laboratory of Ophthalmology, University of Oxford, U.K.
Osborne
N N
NN
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002924:Ciliary Body / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007498:Iris / Q000378:metabolism*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology
D011985:Receptors, Serotonin; D005576:Colforsin; D012701:Serotonin; C047087:5-carboxamidotryptamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases