Effects of acute thioridazine, metoclopramide and SCH 23390 on the basal activity of A9 and A10 dopamine cells

AbstractLysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism.

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Qualitative and Quantitative MALDI Imaging of the Positron Emission Tomography Ligands Raclopride (a D2 Dopamine Antagonist) and SCH 23390 (a D1 Dopamine Antagonist) in Rat Brain Tissue Sections Using a Solvent-Free Dry Matrix Application Method

Analytical Chemistry ◽

10.1021/ac202630t ◽

2011 ◽

Vol 83 (24) ◽

pp. 9694-9701 ◽

Cited By ~ 61

Author(s):

Richard J. A. Goodwin ◽

C. Logan Mackay ◽

Anna Nilsson ◽

David J. Harrison ◽

Lars Farde ◽

...

Keyword(s):

Positron Emission Tomography ◽

Rat Brain ◽

Sch 23390 ◽

Emission Tomography ◽

Dopamine Antagonist ◽

Maldi Imaging ◽

Qualitative And Quantitative ◽

Tissue Sections ◽

Positron Emission ◽

Rat Brain Tissue

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DA1 dopamine receptors in renal cortical collecting duct

AJP Renal Physiology ◽

10.1152/ajprenal.1991.261.5.f890 ◽

1991 ◽

Vol 261 (5) ◽

pp. F890-F895 ◽

Cited By ~ 2

Author(s):

K. Ohbu ◽

R. A. Felder

Keyword(s):

Adenylate Cyclase ◽

Specific Binding ◽

Collecting Duct ◽

Sch 23390 ◽

Receptor Density ◽

Cortical Collecting Duct ◽

Tightly Coupled ◽

Renal Dopamine ◽

Dissociation Constant Kd ◽

Stimulation Of

Renal dopamine DA1 receptors are linked to the regulation of sodium transport. We have previously reported the presence of DA1 receptors in the proximal convoluted tubule (PCT) but not in the distal convoluted tubule. However, the DA1 receptor in the collecting duct, the final determinant of electrolyte transport, has not been studied. DA1 receptors were studied in the microdissected cortical collecting duct (CCD) of rats by autoradiography with use of the selective DA1 radioligand 125I-Sch 23982 and by measurement of adenylate cyclase (AC) activity. Specific binding of 125I-Sch 23982 to CCD was saturable with radioligand concentration. The dissociation constant (Kd) was 0.46 +/- 0.08 nM (n = 5), and the maximum receptor density (Bmax) was 1.41 +/- 0.43 fmol/mg protein (n = 5). The DA1 antagonist Sch 23390 was more effective than the DA1 agonist fenoldopam in competing for specific 125I-Sch 23982 binding. Fenoldopam stimulated AC activity in CCD in a concentration-dependent (10(-9)-10(-6) M) manner. The ability of fenoldopam to stimulate AC activity was similar in CCD and PCT even though DA1 receptor density was 1,000 times greater in the CCD than in the PCT. In additional studies, fenoldopam stimulation of AC activity did not influence vasopressin-stimulated AC activity. We conclude that the DA1 receptor in rat CCD is tightly coupled to AC stimulation and that there is no interaction between DA1 agonist-stimulated and vasopressin-stimulated AC activity in the CCD.

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SCH 23390, but not raclopride, decreases intake of intraorally infused 10% sucrose

Appetite ◽

10.1016/0195-6663(92)90151-u ◽

1992 ◽

Vol 19 (2) ◽

pp. 223 ◽

Cited By ~ 1

Author(s):

A. Tyrka ◽

G.P. Smith

Keyword(s):

Sch 23390

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Homogeneity and long-term stability of tetracycline-regulated gene expression with low basal activity by using the rtTA2S-M2 transactivator and insulator-flanked reporter vectors

Gene ◽

10.1016/j.gene.2003.10.029 ◽

2004 ◽

Vol 327 (1) ◽

pp. 61-73 ◽

Cited By ~ 22

Author(s):

Zhican Qu ◽

Jaideep V Thottassery ◽

Sabrina Van Ginkel ◽

Marina Manuvakhova ◽

Louise Westbrook ◽

...

Keyword(s):

Gene Expression ◽

Term Stability ◽

Long Term Stability ◽

Basal Activity ◽

Regulated Gene Expression

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Seminalplasmin. An endogenous calmodulin antagonist

Biochemical Journal ◽

10.1042/bj2300277 ◽

1985 ◽

Vol 230 (1) ◽

pp. 277-280 ◽

Cited By ~ 11

Author(s):

K Gietzen ◽

H J Galla

Keyword(s):

Basic Protein ◽

Electrostatic Forces ◽

High Potency ◽

Calmodulin Antagonist ◽

Basal Activity ◽

Bull Semen ◽

Stimulation Of

Seminalplasmin, a strongly basic protein isolated from bull semen, was found to antagonize with high potency and extraordinary specificity the function of calmodulin. Calmodulin antagonism is the result of an interaction between the two proteins, which is mainly determined by electrostatic forces. The stimulation of Ca2+-transporting ATPase and phosphodiesterase by calmodulin was half-maximally inhibited at approx. 0.1 microM-seminalplasmin. However, the basal activity of calmodulin-dependent enzymes was not significantly altered by seminalplasmin over the concentration range investigated.

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