AUTORADIOGRAPHY OF SEROTONIN 5-HT1A RECEPTOR-ACTIVATED G-PROTEINS IN GUINEA-PIG BRAIN SECTIONS BY AGONIST-STIMULATED [S-35] GTP-GAMMA-S BINDING

G protein activation mediated by serotonin 5-HT1A and 5-HT1B/D recepto rs in guinea pig brain was investigated by using quantitative autoradi ography of agonist-stimulated [S-35]GTP gamma S binding to brain secti ons, [S-35]GTP gamma S binding was stimulated by the mixed 5-HT1A/5-HT 1B/D agonist L694247 in brain structures enriched in 5-HT1A binding si tes, i.e., hippocampus (+140 +/- 14%), dorsal raphe (+70 +/- 8%), late ral septum (+52 +/- 12%), cingulate (+36 +/- 8%), and entorhinal corte x (+34 +/- 5%), L694247 caused little or no stimulation of [S-35] GTP gamma S binding in brain regions with high densities of 5-HT1B/D bindi ng sites (e.g., substantia nigra, striatum, central gray, and dorsal s ubiculum). The [S-35]GTP gamma S binding response was antagonized by W AY100635 (10 mu M) and methiothepin (10 mu M). In contrast, the 5-HT1B inverse agonist SB224289 (10 mu M) did not affect the L694247-mediate d [S-35]GTP gamma S binding response, and the mixed 5-HT1B/D antagonis t GR127935 (10 mu M) yielded a partial blockade. The distribution patt ern of the [S-35]GTP gamma S binding response and the antagonist profi le suggest the L694247-mediated response in guinea pig brain to be med iated by 5-HT1A receptors. In addition to L694247, 8-hydroxy-2-(di-n-p ropylamino) tetralin, and flesinoxan also stimulated [S-35]GTP gamma S binding; their maximal responses varied between 46 and 52% compared w ith L694247, irrespective of the brain structure being considered. Sum atriptan, rizatriptan, and zolmitriptan (10 mu M) stimulated [S-35]GTP gamma S binding in the hippocampus by 20-50%, Naratriptan, CP122638, and dihydroergotamine stimulated [S-35]GTP gamma S binding to a simila r level as L694247 in hippocampus, lateral septum, and dorsal raphe. I t appears that under the present experimental conditions, G protein ac tivation through 5-HT1A but not 5-HT1B/D receptors can be measured in guinea pig brain sections.