Amygdaloid D1 Receptors Are Not Linked to Stimulation of Adenylate Cyclase

Sarah K. Leonard, Carl M. Anderson, Jean E. Lachowicz, David W. Schulz, Clinton D. Kilts, Richard Mailman

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

In contrast to the classic signal transduction of D1 dopamine receptors in striatum or molecular expression systems, it has been reported that D1 receptor agonists do not stimulate adenylate cyclase in homogenates of microdissected nuclei of the amygdaloid complex. This article examines this phenomenon in detail to determine if lack of cAMP signaling in the amygdaloid complex is an experimental artifact, or an indication of a marked difference from the well-studied basal ganglia terminal fields. Thus, whereas dopamine agonists failed to increase cAMP synthesis in the amygdala, forskolin, guanine nucleotides, or Mg2+ were able to stimulate adenylate cyclase activity in the same preparations. Under several different conditions, caudate preparations responded more robustly than amygdaloid preparations, while amygdala homogenates exhibited higher basal production of cAMP. Whereas the β-adrenergic agonist isoproterenol was able to stimulate cAMP efflux in membranes from both the caudate and amygdala under a variety of tested conditions, neither dopamine nor fenoldopam (D1 agonist) could stimulate adenylate cyclase in the amygdala. Additionally, while manipulation of Ca2+ and calmodulin affected the differential actions of dopamine in the caudate, no change in these parameters restored sensitivity to dopamine in the amygdala. Together, these data challenge the commonly accepted notion that cAMP is a mandatory signaling pathway for D 1 receptors. Because it is now proven that G protein-coupled receptors can signal promiscuously, elucidation of the non-cAMP-dependent signaling mechanisms resulting from D1 activation is clearly critical in understanding how this important receptor functions in situ.

Original languageEnglish (US)
Pages (from-to)320-333
Number of pages14
JournalSynapse
Volume50
Issue number4
DOIs
StatePublished - Dec 15 2003

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Amygdala
Adenylyl Cyclases
Dopamine
Fenoldopam
Dopamine D1 Receptors
Adrenergic Agonists
Guanine Nucleotides
Dopamine Agonists
Colforsin
Calmodulin
G-Protein-Coupled Receptors
Basal Ganglia
Isoproterenol
Artifacts
Signal Transduction
Membranes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Leonard, S. K., Anderson, C. M., Lachowicz, J. E., Schulz, D. W., Kilts, C. D., & Mailman, R. (2003). Amygdaloid D1 Receptors Are Not Linked to Stimulation of Adenylate Cyclase. Synapse, 50(4), 320-333. https://doi.org/10.1002/syn.10272
Leonard, Sarah K. ; Anderson, Carl M. ; Lachowicz, Jean E. ; Schulz, David W. ; Kilts, Clinton D. ; Mailman, Richard. / Amygdaloid D1 Receptors Are Not Linked to Stimulation of Adenylate Cyclase. In: Synapse. 2003 ; Vol. 50, No. 4. pp. 320-333.
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Leonard, SK, Anderson, CM, Lachowicz, JE, Schulz, DW, Kilts, CD & Mailman, R 2003, 'Amygdaloid D1 Receptors Are Not Linked to Stimulation of Adenylate Cyclase', Synapse, vol. 50, no. 4, pp. 320-333. https://doi.org/10.1002/syn.10272

Amygdaloid D1 Receptors Are Not Linked to Stimulation of Adenylate Cyclase. / Leonard, Sarah K.; Anderson, Carl M.; Lachowicz, Jean E.; Schulz, David W.; Kilts, Clinton D.; Mailman, Richard.

In: Synapse, Vol. 50, No. 4, 15.12.2003, p. 320-333.

Research output: Contribution to journalArticle

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Leonard SK, Anderson CM, Lachowicz JE, Schulz DW, Kilts CD, Mailman R. Amygdaloid D1 Receptors Are Not Linked to Stimulation of Adenylate Cyclase. Synapse. 2003 Dec 15;50(4):320-333. https://doi.org/10.1002/syn.10272