Psychiatry related information on Adcy8

• ABSTRACT : BACKGROUND : The Ca2+/calmodulin-stimulated adenylyl cyclase (AC) isoforms AC1 and AC8, couple NMDA receptor activation to cAMP signaling pathways in neurons and are important for development, learning and memory, drug addiction and persistent pain [1].

High impact information on Adcy8

• Here we show that wild-type, AC1, AC8, or AC1&8 double knockout (DKO) mice were indistinguishable in tests of acute pain, whereas behavioral responses to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant, were reduced or abolished in AC1&8 DKO mice [2].
• AC1 and AC8 are highly expressed in the anterior cingulate cortex (ACC), and contribute to inflammation-induced activation of CREB [2].
• By generating transgenic mice whose expression of beta-galactosidase is controlled by the AC8 5'-flanking DNA sequences, we demonstrate that the DNA sequences within the 10 kb preceding exon 1 are critical for establishment of this region-specific pattern [3].
• By in situ hybridization, we have found the highest expression of AC8 mRNA within the olfactory bulb, thalamus, habenula, cerebral cortex, and hypothalamic supraoptic and paraventricular nuclei [3].
• A cloned, virus-producing, tumorigenic, promonocytic leukemia cell line, AC8, derived from an Abelson murine leukemia virus-infected mouse can differentiate in vitro [4].

Biological context of Adcy8

• AC8 gene expression also begins early in embryonic life (E12)--but in a more limited number of regions than in adults [5].
• Here, we have used the N terminus of AC8 as a bait in a yeast two-hybrid screen of a human embryonic kidney (HEK) 293 cell cDNA library and identified the catalytic subunit of the serine/threonine protein phosphatase 2A (PP2A(C)) as a binding partner [6].
• PKA-mediated phosphorylation did not influence either calmodulin or PP2A(C) association with AC8 [6].
• AC8 transgenic mice thus represent an original model to investigate the relative influence of Ca(2+) and cAMP on cardiac function within a phenotype of enhanced cardiac contractility and relaxation [7].

Anatomical context of Adcy8

• AC1 and AC8 in the anterior cingulate cortex (ACC) and the spinal cord were previously shown to be important in subcutaneous inflammatory pain [1].
• Adenylyl cyclases 1 (AC1) and 8 (AC8) are the two major calcium-stimulated ACs in the central nervous system [8].
• A transient peak of AC8 expression is found in layer IV of the somatosensory cortex [5].
• Thus, only AC1 is required for the maturation of the retinal axon terminals whereas AC5 and AC8 are not needed [9].
• At that time, the other calcium-stimulated AC, AC8, is expressed in the superior colliculus (SC) but not in the RGCs [10].

Associations of Adcy8 with chemical compounds

• Here, we report that genetic deletion of AC1 significantly attenuated neuronal death induced by glutamate in primary cultures of cortical neurons, whereas AC8 deletion did not produce a significant effect [8].
• Cortical lesions induced by NMDA were significantly reduced in AC1 but not in AC8 knock-out mice [8].
• Spatiotemporal localization of the calcium-stimulated adenylate cyclases, AC1 and AC8, during mouse brain development [5].
• Seemingly, a protein, glycoprotein, and carbohydrate were recognized by MAB E6, FE10, and AC8, respectively [11].
• Cyclic AMP compartmentation due to increased cAMP-phosphodiesterase activity in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8) [12].

Other interactions of Adcy8

• Therefore, we conducted the present work to test the role of AC1 and AC8 in both acute persistent and chronic muscle pain [1].
• Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement [13].
• Of particular interest were AC3 and AC8, located in the same regions as, and hence possibly directly associated with, specific cell surface receptors and G proteins that are able to regulate the spermatozoon's acquisition and maintenance of fertilizing ability via changes in AC/cAMP [14].
• In contrast, AC8 KO and DKO mice, but not AC1 KO mice, demonstrate decreased voluntary ethanol consumption compared with WT mice [15].

Analytical, diagnostic and therapeutic context of Adcy8

• Mice lacking either AC1 or AC8 genes or DKO did not differ from wild-type mice in short-term antinociceptive responses to morphine measured in the tail-flick analgesia assay [16].

References