PHARMACOLOGICAL CHARACTERIZATION OF A SEROTONIN RECEPTOR INVOLVED IN AN EARLY EMBRYONIC BEHAVIOR OF HELISOMA-TRIVOLVIS

In contrast to the abundance of information on the many physiological and developmental actions of serotonin in molluscan nervous systems, c omparatively little is known about the serotonin receptors involved in these responses. Embryos of the pulmonate gastropod, Helisoma trivolv is, display a cilia-driven rotational behavior that is regulated by en dogenous serotonin. In the present study, two functional assays were u sed to determine some of the pharmacological properties of the recepto rs that mediate the cilio-excitatory action of serotonin. Time-lapse v ideo microscopy was used to measure whole embryo rotation rate and cil ia beat frequency in isolated cells. In dose-response experiments, ser otonin was approximately 10 times more potent in stimulating cilia bea t frequency over embryo rotation. In rotation experiments, 5-carboxyam idotryptamine and methysergide had effective agonist activity in dose ranges similar to that of serotonin (1 to 100 mu M). In contrast, 8-hy droxydipropylaminotetralin HBr (8-OH-DPAT) displayed agonist activity of lower potency and effectiveness. Several compounds displayed antago nist activity in the 1 to 100 mu M dose range, including mianserin, sp iperone, ritanserin, 1-(1-naphthyl) piperazine, and propranolol. alpha -Methylserotonin had mixed agonist-antagonist activity, and metoclopra mide, MDL-72222, and ketanserin were inactive. Experiments on isolated cells suggested that the extremely effective antagonism displayed by mianserin in the embryo rotation assay was due to its specific activit y at ciliary serotonin receptors. These results implicate the presence of a novel serotonin receptor on embryonic ciliated cells that is pha rmacologically distinct from those previously characterized in vertebr ate or invertebrate systems. (C) 1994 John Wiley and Sons, Inc.