Histamine H3 receptor activation inhibits dopamine D1 receptor-induced cAMP accumulation in rat striatal slices

• Published in: Neuroscience letters Vol. 364; no. 3; pp. 179 - 184
• Main Authors: SANCHEZ-LEMUS, Enrique, ARIAS-MONTANO, José-Antonio
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 08.07.2004
• Subjects: Animals; Biological and medical sciences; Corpus Striatum - metabolism; Cyclic AMP - metabolism; Fundamental and applied biological sciences. Psychology; Male; Neurons - metabolism; Organ Culture Techniques; Rats; Rats, Wistar; Receptors, Dopamine D1 - metabolism; Receptors, Histamine H3 - metabolism; Vertebrates: nervous system and sense organs; H3 receptor; H3 histamine receptor; Basal ganglia; Rat; D1 receptor; Rodentia; Central nervous system; D1 Dopamine receptor; Cyclic AMP; Corpus striatum; Basal ganglion; cAMP; Encephalon; Histamine; Striatum; Vertebrata; Mammalia; Animal; Biological accumulation; Biological receptor
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2004.04.045

In striatal membranes bearing significant levels of histamine H3 receptors (72 +/- 14 fmol/mg protein), the H3 agonist immepip (1 microM) increased [35S]GTPgammaS binding to 119 +/- 2% of basal, an effect prevented by the H3 antagonist clobenpropit and by pre-treatment with pertussis toxin. In slices labelled with [3H]adenine and in the presence of 1 mM isobutylmethylxantine (IBMX), the selective dopamine D1-like (D1/D5) receptor agonist SKF-81297 stimulated cyclic [3H]AMP ([3H]cAMP) accumulation (maximal stimulation 205 +/- 24% of basal, EC50 113 +/- 12 nM), an effect fully blocked by the D1/D5 antagonist SCH-23390. The accumulation of [3H]cAMP induced by 1 microM SKF-81297 was inhibited in a concentration-dependent manner by the selective H3 receptor agonist immepip (maximal inhibition 60+/-5%, IC50 13 +/- 5 nM). The inhibitory action of 100 nM immepip was reversed in a concentration-dependent manner by the H3 antagonist thioperamide (EC50 13 +/- 3 nM, Ki 1.4 +/- 0.3 nM). Forskolin-induced [3H]cAMP accumulation (726 +/- 57% of basal) was also reduced by H3 receptor activation, although to a lesser extent (19.1 +/- 3.2% inhibition), an action not affected by the absence of either IBMX or Ca2+ ions in the incubation medium. Neither the density of [3H]SCH-23390 binding sites (D1 receptors) nor the inhibition by SKF-81297 were affected by 1 microM immepip, ruling out a direct interaction between D1 and H3 receptors. These results indicate that through H3 receptors coupled to Galphai/o proteins, histamine modulates cAMP formation in striatal neurones that possess D1 receptors, most probably GABAergic striato-nigral neurones.