Premium
GH 4 ZD10 cells expressing rat 5‐HT 1A receptors coupled to adenylyl cyclase are a model for the postsynaptic receptors in the rat hippocampus
Author(s) -
Fowler C.J.,
Ahlgren P.C.,
Brännström G.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14476.x
Subject(s) - medicine , endocrinology , chemistry , ipsapirone , agonist , 5 ht receptor , receptor , 8 oh dpat , spiperone , serotonin , biology , biochemistry
1 Vasoactive intestinal polypeptide (VIP) stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) production by cultured GH 4 ZD10 cells with an EC 50 value of about 7 n m . The extracellularly recovered cyclic AMP predominated, and was reduced by co‐incubation with 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and 5‐hydroxytryptamine (5‐HT), whereas dopamine (0.1–30 μ m ) did not reduce VIP‐stimulated cyclic AMP production. 2 The responses to 5‐HT and 8‐OH‐DPAT were blocked by (−)‐alprenolol and NAN 190. The antagonism by (−)‐alprenolol was competitive in nature with a pA 2 value of 7.0. 3 The responsiveness of the cells to 5‐HT agonists was highly dependent upon the culturing conditions used. Thus, 8‐OH‐DPAT inhibition of VIP (30 n m )‐stimulated cyclic AMP production decreased with increasing passage number of the cells. Reduction of the zinc concentration used to promote expression of the 5‐HT 1A receptor gene produced a greater sensitivity of the cells to 5‐HT agonists. 4 Under such conditions, the following efficacies (5‐HT = 100) were found: lisuride 106, (+)‐lysergic‐acid diethylamide 100, 5‐methoxy‐N,N‐dimethyltryptamine 98, RU 24949 98, 5‐carboxamidotryptamine 97, (±)‐8‐OH‐DPAT 90, (+)‐8‐OH‐DPAT 87, 1‐[2‐(4‐aminophenyl)ethyl]‐4‐(3‐trifluoromethylphenyl)‐piperazine 86, flesinoxan 79/88, (−)‐8‐OH‐DPAT 62, buspirone 43/50, ipsapirone 46. Spiroxatrine and spiperone had a low intrinsic activity, but reduced the response to 5‐HT. These efficacies are similar to those reported in the literature for post‐synaptically localized 5‐HT 1A receptors in the rat hippocampus. Thus, the GH 4 ZD10 cells serve as a useful in vitro model system for these receptors.