Lee, KW Hong, JH Choi, IY Che, YZ Lee, JK Yang, SD Song, CW Kang, HS Lee, JH Noh, JS Shin, HS Han, PL 2024-01-21T10:05:28Z 2024-01-21T10:05:28Z 2021-09-01 2002-09-15 0270-6474 https://pubs.kist.re.kr/handle/201004/139208 Dopamine receptor subtypes D-1 and D-2, and many other seven-transmembrane receptors including adenosine receptor A(2A), are colocalized in striatum of brain. These receptors stimulate or inhibit adenylyl cyclases (ACs) to produce distinct physiological and pharmacological responses and interact with each other synergistically or antagonistically at various levels. The identity of the AC isoform that is coupled to each of these receptors, however, remains unknown. To investigate the in vivo role of the type 5 adenylyl cyclase (AC5), which is preferentially expressed in striatum, mice deficient for the AC5 gene were generated. The genetic ablation of the AC5 gene eliminated >80% of forskolin-induced AC activity and 85-90% of AC activity stimulated by either D-1 or A(2A) receptor agonists in striatum. However, D-1- or A(2A)-specific pharmaco-behaviors were basically preserved, whereas the signal cascade from D-2 to AC was completely abolished in AC5(-/-), and motor activity of AC5(-/-) was not suppressed by treatment of cataleptic doses of the antipsychotic drugs haloperidol and sulpiride. Interestingly, both haloperidol and clozapine at low doses remarkably increased the locomotion of AC5(-/-) in the open field test that was produced in part by a common mechanism that involved the increased activation of D-1 dopamine receptors. Together, these results suggest that AC5 is the principal AC integrating signals from multiple receptors including D-1, D-2, and A(2A) in striatum and the cascade involving AC5 among diverse D-2 signaling pathways is essential for neuroleptic effects of antipsychotic drugs. English SOC NEUROSCIENCE CENTRAL-NERVOUS-SYSTEM MUSCARINIC ACETYLCHOLINE PREFRONTAL CORTEX DEFICIENT MICE EXPRESSION MULTIPLE GENE INHIBITION PROTEIN BRAIN Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase Article 1 JOURNAL OF NEUROSCIENCE, v.22, no.18, pp.7931 - 7940 JOURNAL OF NEUROSCIENCE 22 18 7931 7940 scie scopus 000177916000013 2-s2.0-0037107119 Neurosciences Neurosciences & Neurology Article CENTRAL-NERVOUS-SYSTEM MUSCARINIC ACETYLCHOLINE PREFRONTAL CORTEX DEFICIENT MICE EXPRESSION MULTIPLE GENE INHIBITION PROTEIN BRAIN AC5 dopamine receptors knock-out mice antipsychotics striatum adenylyl cyclase cAMP adenosine receptors