PHARMACOLOGICAL MODULATION OF IMMUNOREACTIVE IMIDAZOLINE RECEPTOR PROTEINS IN RAT-BRAIN - RELATIONSHIP WITH NON-ADRENOCEPTOR [H-3] IDAZOXANBINDING-SITES

1 The densities of various imidazoline receptor proteins (with apparen t molecular masses of approximate to 29/30- 45- and 66-kDa) were quant itated by immunoblotting in the rat cerebral cortex after various drug treatments. The modulation of these imidazoline receptor proteins was then compared with the changes in the density of non-adrenoceptor [H- 3]-idazoxan binding sites (I-2-sites) induced by the same drug treatme nts. 2 Chronic treatment (7 days) with the I-2-selective imidazol(in)e drugs idazoxan (10 mg kg(-1)), cirazoline (1 mg kg(-1)) and LSL 60101 (10 mg kg(-1)) differentially increased the immunoreactivity of imida zoline receptor proteins. The levels of the 29/30-kDa protein were inc reased by idazoxan and LSL 60101 (23%), the levels of the 45-kDa prote in only by cirazoline (44%) and those of the 66-kDa protein only by id azoxan (50%). These drug treatments also increased the density of I-2- sites (32-42%). 3 Chronic treatment (7 days) with efaroxan (10 mg kg(- 1)), RX821002 (10 mg kg(-1)) and yohimbine (10 mg kg(-1)), which posse ss very low affinity for I-2-imidazoline receptors, did not alter eith er the immunoreactivity of imidazoline receptor proteins or the densit y of I-2-sites. 4 Chronic treatment (7 days) with the monoamine oxidas e (MAO) inhibitors clorgyline (10 mg kg(-1)) and phenelzine (10 mg kg( -1)) decreased the immunoreactivity of the 29/30-kDa (17-24%), 45-kDa (19%) and 66-kDa (23-31%) imidazoline receptor proteins. The alkylatin g agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (1.6 mg kg(-1) 6 h) also decreased the levels of the three imidazoline receptor prote ins (20-47%). These drug treatments consistently decreased the density of I-2-sites (31-57%). 5 Significant correlations were found when the mean percentage changes in immunoreactivity of imidazoline receptor p roteins were related to the mean percentage changes in the density of I-2-sites after the various drug treatments (r = 0.92 for the 29/30-kD a protein, r = 0.69 for the 45-kDa protein and r = 0.75 for the 66-kDa protein). 6 In the rat cerebral cortex the I-2-imidazoline receptor l abelled by [H-3]-idazoxan is heterogeneous in nature and the related i midazoline receptor proteins (29/30-, 45- and 66-kDa) detected by immu noblotting contribute differentially to the modulation of I-2-sites af ter drug treatment.