CLONING, EXPRESSION, PHARMACOLOGY AND TISSUE DISTRIBUTION OF THE MOUSE SOMATOSTATIN RECEPTOR SUBTYPE 5

The gene encoding the mouse somatostatin receptor subtype 5 has been i solated from a genomic library and the mRNA start point mapped to posi tion -95 relative to the translational start codon. The promoter regio n is devoid of TATA and CAAT boxes but contains putative binding sites for AP-I, AP-2 and SP1 and response elements for glucocorticoids (GRE ) and phorbol esters (TRE), The encoded receptor protein with a predic ted molecular weight of 42.5 kDa is comprised of 385 amino acids and t hus contains 22 and 21 amino acids more than rat and human counterpart s. The extra amino acids are caused by another translational initiatio n codon located further upstream. In the region of overlap the mouse s omatostatin receptor subtype 5 displays 96.7% sequence identity to the rat and 81.7% to the human homologue, Application of somatostatin-14 and -28 to human embryonic kidney cells expressing the recombinant rec eptor resulted in the inhibition of forskolin-stimulated adenylyl cycl ase with comparable EC50 values. Consistent with the observed sequence relationship, the mouse somatostatin receptor subtype 5 displays a ph armacological profile that resembles the rat homologue more closely th an the human counterpart. mRNA for the mouse somatostatin type 5 recep tor has been detected in pituitary, kidney, spleen and ovary and, to a lesser extent, in brain, stomach, intestine and thymus but was not ob served in heart, pancreas and liver.