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Regulation of adenylate cyclase type VIII splice variants by acute and chronic Gi/o-coupled receptor activation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Steiner, Debora Avidor-Reiss, Tomer Schallmach, Ester Butovsky, Elena Lev, Nirit Vogel, Zvi |
| Copyright Year | 2005 |
| Abstract | We previously reported that acute agonist activation of G(i/o)-coupled receptors inhibits adenylate cyclase (AC) type VIII activity, whereas agonist withdrawal following chronic activation of these receptors induces AC-VIII superactivation. Three splice variants of AC-VIII have been identified, which are called AC-VIII-A, -B and -C (with AC-VIII-B missing the glycosylation domain and AC-VIII-C lacking most of the C1b area). We report here that AC-VIII-A and -B, but not -C, are inhibited by acute mu-opioid and dopaminergic type D2 receptor activation, indicating that the C1b area of AC-VIII has an important role in AC inhibition by G(i/o)-coupled receptor activation. On the other hand the glycosylation sites in AC-VIII did not play a role in AC-VIII regulation. Although AC-VIII-A and -C differed in their capacity to be inhibited by acute agonist exposure, agonist withdrawal after prolonged treatment led to a similar superactivation of all three splice variants, with no significant change in AC-VIII expression. AC-VIII superactivation was not affected by pre-incubation with a cell permeable cAMP analogue, indicating that the superactivation does not depend on the agonist-induced reduction in cAMP levels. The superactivated AC-VIII-A, -B and -C were similarly re-inhibited by re-application of agonist (morphine or quinpirole), returning the activity to control levels. These results demonstrate marked differences in the agonist inhibition of the AC-VIII splice variants before, but not after, superactivation. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.biochemj.org/content/ppbiochemj/386/2/341.full.pdf |
| PubMed reference number | 15537392v1 |
| Volume Number | 386 |
| Part | 2 |
| Journal | The Biochemical journal |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 8-chloro-cyclic adenosine monophosphate Adenylate Cyclase Adenylyl Cyclase 9 Analog Dopamine D2 Receptor Dopamine Hydrochloride Morphine Quinpirole Receptor Activation Process |
| Content Type | Text |
| Resource Type | Article |