Disease relevance of Adcy3

• Since alterations in the expression of AC III were recently reported in the GK rat (a model of non-insulin-dependent diabetes mellitus, NIDDM), we also have analyzed the mRNA expression of Galphaolf and AC isoforms in pancreatic islets from GK rats and from adult rats neonatally treated by streptozotocin (nSTZ rats), another model of NIDDM [1].
• Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation [2].

High impact information on Adcy3

• In mammalian germ cells, cAMP signaling is dependent on two forms of adenylyl cyclase, the conventional membrane-bound ACIII and a soluble form of adenylyl cyclase (sAC) [3].
• It was associated with the presence of two point mutations identified at positions -28 bp (A --> G) and -358 bp (A --> C) of the promoter region of the AC-III gene and was demonstrable in both GK rat islets and peripheral blood cells [4].
• This is linked to overexpression of AC-III mRNA in GK islets due to two functional point mutations in the promoter region of the AC-III gene [4].
• Transfection of COS cells with a luciferase reporter gene system revealed up to 25-fold increased promoter activity of GK AC-III promoter when compared with normal rat promoter (P < 0.0001) [4].
• Furthermore, mouse oocytes deficient in AC3 show signs of a defect in meiotic arrest in vivo and accelerated spontaneous maturation in vitro [5].

Biological context of Adcy3

• Ribonuclease protection studies confirmed that ACIII transcripts are present in germ cells, appear during the meiotic prophase, and accumulate during spermiogenesis [6].
• Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression [2].

Anatomical context of Adcy3

• These regulations of cAMP levels indicate that the major cyclase that produces cAMP in the rat oocyte has properties identical to those of recombinant or endogenous AC3 expressed in somatic cells [5].
• These regulatory characteristics of AC activity are consistent with the molecular identification of ACs indicating the presence of AC3 in luteal cells [7].
• A Northern blot analysis performed on total testis RNA demonstrated the presence of a predominant transcript of 7.5 kb, suggesting that the ACIII expressed in germ cells may derive from a splicing variant different from the 4.5 kb transcripts expressed in somatic cells [6].
• Immunofluorescence localization of this protein in the seminiferous tubules showed that ACIII was predominantly expressed in postmeiotic germ cells from round spermatids in the cap phase to maturing elongating spermatids [6].
• The spatial and temporal expression of ACIII in germ cells indicates a role of this AC in the acrosome formation [6].

Associations of Adcy3 with chemical compounds

• Stimulation of cAMP levels by agents that increase Ca(2+) in native cells was consistent with the expression of AC3, but overexpression of AC6, which is inhibited by Ca(2+), blunted the Ca(2+)-stimulable cAMP response [8].
• Molecular identification of adenylyl cyclase 3 in bovine corpus luteum and its regulation by prostaglandin F2alpha-induced signaling pathways [7].
• In contrast, culture at 11 mM glucose decreased relative AC-III, -V and -VI mRNA levels by as much as 50% [9].
• In contrast, such an enhanced postsynaptic dopamine D1 receptor efficacy did not occur 1-3 days following repeated morphine administration, but appeared to develop slowly resulting in a profound increase of dopamine-sensitive adenylate cyclase 3 weeks after the last injection [10].
• The increase in AC-III expression was paralleled by an increase in isoproterenol-stimulated AC activity [11].

Other interactions of Adcy3

• This strategy yielded high-frequency amplification of a complementary DNA (cDNA) identical to type III AC (ACIII), a form previously identified as the major adenylyl cyclase expressed in the olfactory system [6].
• The steady-state mRNA levels of AC II and AC III were clearly increased in the islets of the two rat models of NIDDM [1].

Analytical, diagnostic and therapeutic context of Adcy3

• The mRNA coding for the AC3 isoform of adenylyl cyclase was detected in rat and mouse oocytes by RT-PCR and by in situ hybridization [5].
• The expression of AC3 protein was confirmed by immunocytochemistry and immunofluorescence analysis in oocytes in situ [5].
• To determine whether these RNAs are translated into a protein, Western blot analysis was performed using an antibody specific for the carboxyl terminus of ACIII [6].
• Direct hybridization and polymerase chain reaction analyses demonstrated that BAT expresses messenger RNAs (mRNAs) encoding AC-III, AC-IV, AC-V, and AC-VI subtypes [12].
• Analysis of AC mRNAs by nuclease protection assay demonstrated the presence of mRNAs encoding AC-III, AC-IV, AC-VI, and AC-IX in embryonic and postnatal BAT [11].

References