CLONING AND EXPRESSION OF A 5HT7 RECEPTOR FROM XENOPUS-LAEVIS

A clone encoding a 5TH7 receptor, XM2, has been isolated from Xenopus laevis. The mRNA encoding XM2 is expressed in brain, liver, muscle, ki dney, intestine and skin, but not in heart or lung. Co-expression of X M2 and the cystic fibrosis transmembrane conductance regulator (CFTR) in Xenopus oocytes demonstrated coupling of the receptor and the chann el via the protein kinase A pathway. A rank order of potency was obtai ned for serotonergic agonists of 5-hydroxytryptamine (5HT) greater tha n or equal to 5-methoxytryptamine (5MeOxyT) greater than or equal to a lpha-methyl-5-hydroxytryptamine (alpha MeSHT) > 8-OH-DPAT, and for ser otonergic antagonists of ritanserin > NAN190 > mesulergine not equal p indolol. Thus, XM2 encodes a 5HT receptor with sequence homology to ma mmalian 5HT7 receptors, a similar intracellular signal transduction an d receptor pharmacology, but a broader distribution in peripheral tiss ues.