Regulation of adenylate cyclase type VIII splice variants by acute and chronic Gi/o-coupled receptor activation

Debora Steiner, Tomer Avidor-Reiss, Ester Schallmach, Elena Butovsky, Nirit Lev, Zvi Vogel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 μ-opioid and dopaminergic type D2 receptor activation, indicating that the C1b area of AC-VIII has an important role in AC inhibition by Gi/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.

Original languageEnglish
Pages (from-to)341-348
Number of pages8
JournalBiochemical Journal
Issue number2
StatePublished - 1 Mar 2005
Externally publishedYes


  • Adenylate cyclase type VIII
  • CAMP
  • Dopamine receptor
  • G-protein-coupled receptor
  • Opiate receptor
  • Superactivation


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