Copyright C I) \ The American Society for Pharmanlogy and Experimental Therapeutics All rights of reproduction in any form reserved. MOLECULAR puARMAcoI.o(;, 37:622-630 Serotonin-2 Receptors Coupled to Phosphoinositide Hydrolysis

A permanent line of cells has been established from the trans-plantable rat pituitary tumor 731 5a. P1 1 cells have been cloned repeatedly, and after more than 60 passages their growth and characteristics are stable. Results of radioligand binding studies with 125l-lysergic acid diethylamide (1251-LSD) indicate that P11 cells express serotonin-2 (5-HT2) receptors. Analysis of the binding of 125l-LSD to membranes prepared from P1 1 cells revealed the presence of a single class of high affinity sites (Kd = 1.6 nM; Bmax 21 1 fmol/mg of protein). The pharmacological profile of the inhibition of the binding of 125l-LSD by a panel of drugs was consistent with the expected profile of these drugs at 5-HT2 receptors. The affinity of the site for serotonin was in the low micromolar range and was decreased by GTP. Phos-phoinositide hydrolysis in P1 1 cells, measured in the presence of lithium, was stimulated by serotonin. Increasing concentra