KAPPA-OPIOID RECEPTOR IN HUMANS - CDNA AND GENOMIC CLONING, CHROMOSOMAL ASSIGNMENT, FUNCTIONAL EXPRESSION, PHARMACOLOGY, AND EXPRESSION PATTERN IN THE CENTRAL-NERVOUS-SYSTEM

Using the mouse delta-opioid receptor cDNA as a probe, we have isolate d genomic clones encoding the human mu- and kappa-opioid receptor gene s, Their organization appears similar to that of the human delta recep tor gene, with exon-intron boundaries located after putative transmemb rane domains 1 and 4, The kappa gene was mapped at position q11-12 in human chromosome 8, A full-length cDNA encoding the human kappa-opioid receptor has been isolated. The cloned receptor expressed in COS cell s presents a typical kappa 1 pharmacological profile and is negatively coupled to adenylate cyclase, The expression of kappa-opioid receptor mRNA in human brain, as estimated by reverse transcription-polymerase chain reaction, is consistent with the involvement of kappa-opioid re ceptors in pain perception, neuroendocrine physiology, affective behav ior, and cognition, In situ hybridization studies performed on human f etal spinal cord demonstrate the presence of the transcript specifical ly in lamina II of the dorsal horn, Some divergences in structural, ph armacological, and anatomical properties are noted between the cloned human and rodent receptors.