Immunohistochemical localization of the InsP4 receptor GTPase‐activating protein GAP1IP4BP in the rat brain

Signore, Armando P.; O'Rourke, F; Lu, Xinghua; Feinstein, Maurice B.; Yeh, Hermes H.

doi:10.1002/(sici)1097-4547(19990201)55:3<321::aid-jnr7>3.3.co;2-1

Cited by 1 publication

(1 citation statement)

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“…RASA3 RNA is expressed in different human tissues including brain, skeletal muscles, spleen, peripheral blood leukocytes, and platelets, suggesting roles in all of these tissues (39,40). In the brain, immunoreactivity for RASA3 is highest in the CA1 of the hippocampus, amygdala, cerebellum, and pyriform cortex (41). As discussed above, other G␣ icoupled receptors have the potential to couple to RASA3 to inhibit ERK1/2 activation, and the role of RASA3 may depend on the receptors present.…”

Section: Roles Of D2s Receptor-g␣ I -Rasa3mentioning

confidence: 99%

GAP1(IP4BP)/RASA3 Mediates Gαi-induced Inhibition of Mitogen-activated Protein Kinase

Nafisi¹,

Banihashemi

Daigle

et al. 2008

Journal of Biological Chemistry

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The dopamine D2S receptor (short isoform) couples to inhibitory G␣ i/o proteins to inhibit thyrotropin-releasing hormone (TRH)-stimulated p42/p44 mitogen-activated protein kinase (ERK1/2) phosphorylation in GH4ZR7 rat pituitary cells, consistent with its actions to inhibit prolactin gene transcription and cell proliferation. However, the underlying mechanism is unclear. To identify novel G␣ i effectors, yeast two-hybrid screening of a GH4ZR7 cDNA library was done using constitutively active G␣ i3 -Q204L, and multiple clones of the RasGAP cDNA GAP1 Five dopamine receptor genes are known, and the dopamine-D2 receptor is among the most studied because of its involvement in mental and neurological disorders such as schizophrenia, addiction, and Parkinson disease. In addition, the dopamine-D2 receptor mediates inhibitory regulation of endocrine function, with a primary role in the pituitary to regulate prolactin synthesis, secretion, and lactotroph cell proliferation. For example, in homozygous mice deficient in the gene encoding the D2 receptor or lacking dopamine, pituitary adenoma and hyperprolactinemia occur with age (1-4). Conversely, mice lacking the gene encoding the dopamine transporter show dopamine hypersecretion that leads to pituitary hypotrophy (5). In addition, dopamine-D2 receptor agonists such as bromocryptine or cabergoline are used clinically to induce regression of pituitary adenomas (6 -9). The dopamine D2 receptor gene contains an alternately spliced exon encoding 29 amino acids in the putative third intracellular loop to generate short (D2S) and long (D2L) forms of the receptor (10). Dopamine D2S receptors have been shown to have anti-proliferative actions in pituitary lactotrophs, whereas the D2L receptor did not appear to be anti-proliferative (11). However, the specific signaling mechanisms underlying dopamine D2S actions in pituitary cells remain to be fully elucidated.GH4ZR7 cells are GH4C1 lactotroph cells stably transfected with the dopamine D2S receptor cDNA. These cells provide a useful model to study the signaling of the dopamine-D2S receptor in pituitary cells that retain differentiated properties of lactotrophs. These include expression of receptors that stimulate (thyrotropin-releasing hormone (TRH) 3 receptors) or inhibit (somatostatin and muscarinic receptors) the synthesis and secretion of growth hormone and prolactin (PRL) (12). In GH4ZR7 cells, dopamine inhibits cAMP formation, PRL synthesis and secretion, and cell proliferation. Previously, a novel D2S receptor-mediated inhibition of TRH-induced ERK1/2 activation was identified in these cells (13,14). Interestingly, D2L receptors did not couple to this pathway (15). Activation of ERK1/2 is implicated in TRH induced prolactin transcription (16), and its inhibition is a key pathway for dopamine-D2S-induced inhibition of prolactin transcription (17). This pathway is also observed in primary striatal cultures, suggesting a general role for this D2S receptor-mediated signaling pathway in neuroendocrine tissues (15).

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Section: Roles Of D2s Receptor-g␣ I -Rasa3mentioning

confidence: 99%