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Evidence for the Presence of Serotonin Receptors Negatively Coupled to Adenylate Cyclase in the Rabbit Iris‐Ciliary Body
Author(s) -
Tobin A. B.,
Osborne N. N.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb11758.x
Subject(s) - serotonin , serotonergic , endocrinology , medicine , cyclase , tryptamine , 5 ht receptor , chemistry , forskolin , receptor , biology , stimulation , pharmacology
Serotonin has no obvious effect on basal cyclic AMP levels but reduces the forskolin‐, isoproterenol‐, and vasoactive intestinal peptide‐induced stimulation of cyclic AMP levels in a dose‐dependent manner. Serotonergic, cholinergic, muscarinic, α‐adrenergic, and dopaminergic antagonists have no effect on the serotonin response. Topical Application of a serotonin/pargyline solution to the living eye causes desen‐sitisation of the serotonin response in the iris‐ciliary body, an observation confirming the presence of specific serotonergic receptors linked to adenylate cyclase. The 5‐HT 1A [5‐hy‐droxytryptamine (serotonin) type 1A] receptor agonists 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin and bujspirone mimic the serotonin response in reducing the forskolin‐stimulated cyclic AMP levels, as do the indole derivatives 5‐methoxy‐ tryptamine, 5‐hydroxtryptophan, and tryptamine. However, the ineffectiveness of the 5‐HT 1A agonist ipsapirone and the inability of spiroxatrine to block the serotonin response show that classical 5‐HT 1A receptors are not involved. The serotonin response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor theophylline, which indicates the involvement of an inhibitory guanine regulatory protein in the coupling of the serotonin receptor to the adenylate cyclase catalytic unit.