title: Amygdaloid D1 receptors are not linked to stimulation of adenylate cyclase.
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 beta-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 D1 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.
authors.affiliation: Neuroscience Center, Departments of Psychiatry and Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599-7250, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Leonard
authors.forename: Carl M
authors.initials: CM
authors.lastname: Anderson
authors.forename: Jean E
authors.initials: JE
authors.lastname: Lachowicz
authors.forename: David W
authors.initials: DW
authors.lastname: Schulz
authors.forename: Clinton D
authors.initials: CD
authors.lastname: Kilts
authors.forename: Richard B
authors.initials: RB
authors.lastname: Mailman
mesh_terms: D000255:Adenosine Triphosphate / Q000493:pharmacokinetics; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics; D001665:Binding Sites; D001923:Brain Chemistry; D002147:Calmodulin / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018818:Fenoldopam / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D042282:Microdissection / Q000379:methods; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013460:Sulfur Isotopes / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000318:Adrenergic beta-Agonists; D001552:Benzazepines; D002147:Calmodulin; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D013460:Sulfur Isotopes; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D018818:Fenoldopam; D007545:Isoproterenol; D004298:Dopamine