AUTORADIOGRAPHIC ANALYSIS OF SOMATOSTATIN SRIF(1) AND SRIF(2) RECEPTORS IN THE HUMAN BRAIN AND PITUITARY

The distribution of somatostatin (SRIF) receptor sites was studied by in vitro receptor autoradiography in the human brain and pituitary usi ng the SRIF(1) (sst(2)) receptor selective [I-125]Tyr(3)-octreotide, t he non-subtype selective [I-125]LTT-SRIF-28 ([Leu(8),D-Trp(22) I-125-T yr(25)]SRIF-28) and the SRIF(2)-receptor selective [I-125]CGP 23996 (c [Asu-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) in buffer containing 12 0 mM Na+. SRIF receptor autoradiography was compared with mRNA express ion of somatostatin receptors sst(1-5) as studied by in situ hybridisa tion in human brain. High levels of [I-125]LTT-SRIF-28 and [I-125]Tyr( 3)-octreotide recognition sites were found in the deep layers of cereb ral cortex and molecular layer of cerebellum of the human brain. The h ypothalamus, choroid plexus, most areas of the brainstem and dentate n ucleus were associated with low levels of binding. In contrast to [I-1 25]LTT-SRIF-28 and [I-125]Tyr(3)-octreotide, no difference was observe d for [(125)]]CGP 23996 labelling in the various layers of cerebral co rtex. The choroid plexus, substantia nigra and molecular layer of the cerebellum presented high densities of [I-125]CGP 23996 binding sites whereas no binding was observed in the hypothalamus and locus coeruleu s using this radioligand. Both lobes of the human pituitary displayed low levels of [I-125]LTT-SRIF-28 and [(125)Tyr(3)-octreotide binding. By contrast, the anterior lobe of the pituitary displayed very high le vels of [I-125]CGP 23996 labelled sites whereas intermediate levels we re found in the posterior lobe. There was a partial overlap between ss t(2) receptor mRNA and [I-125]Tyr(3)-octreotide binding, although the distribution of the binding sites was much wider than that of receptor mRNA. The same observation was made for sst(1) and/or sst(4) receptor mRNA and [I-125]CGP 23996 labelled sites. The present data show that SRIF(1) and SRIF(2) receptors are present in the human brain with diff erent distributions, especially in the cerebral cortex and the pituita ry. The very similar distribution of sites labelled with [I-125]LTT-SR IF-28 and [I-125]Tyr(3)-octreotide suggests (i) that sst(2) receptors are predominant within the SRIF(1) family in the human brain and (ii) that [I-125]LTT-SRIF-28 under the conditions used in the present study , does not significantly label SRIF(2) sites.