The Rat SSTR2 Somatostatin Receptor Subtype Is Coupled to Inhibition of Cyclic AMP Accumulation

Strnad, Joann; Eppler, C M; Corbett, M.; Hadcock, John R.

doi:10.1006/bbrc.1993.1312

Cited by 39 publications

(16 citation statements)

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“…5). Similar results were recently obtained by Hadcock and coworkers after expression of rat mSSTR2A in CHO-Kl cells [22]. A possible explanation for these discrepant results is that different G-proteins are expressed in the cells used for transfection.…”

Section: Discussionsupporting

confidence: 87%

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The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B) differ m coupling efficiency to adenylate cyclase and in agonist‐induced receptor desensitization

1993

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The somatostatin receptor 2 (mSSTR2) is alternatively spliced into two isoforms (mSSTR2A and mSSTR2B) which differ at the C-terminus. Both receptors bind somatostatin peptides with a similar high affinity when stably expressed in CHO-Kl cells. However, the spliced form (mSSTR2B) mediates a more efficient inhibition of adenylate cyclase and is much more resistant to agonist-induced reduction of binding than the longer form (mSSTR2A). These findings indicate that alternative splicing may be a physiological mechanism to modulate receptor desensitization and G-protein coupling of mSSTR2.

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Section: Discussionsupporting

confidence: 87%

“…Fax: (49) (89) 599-6216. ate the inhibition of AC. One group failed to observe any effect of mSSTR2A on AC after stable transfection into CHO-DG44 cells or transient transfection into COS-1 or HEK 293 cells [20,21] whereas others found an inhibition of AC after stable transfection into CHOKl cells [22].…”

Section: Introductionmentioning

confidence: 99%

The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B) differ m coupling efficiency to adenylate cyclase and in agonist‐induced receptor desensitization

1993

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“…The inhibition was pertussis toxin-sensitive indicating the coupling of these receptors to pertussis toxin-sensitive G-proteins. Rat SSTR2 and human and mouse SSTR3 have previously been de- cribed to mediate the inhibition of adenylyl cyclase [19,23,46]. In the present study we demonstrated that hSSTR1 and the recently cloned hSSTR4 inhibit adenylyl cyclase activity.…”

Section: Discussionsupporting

confidence: 69%

Distribution and second messenger coupling of four somatostatin receptor subtypes expressed in brain

et al. 1993

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The mRNA distribution m the brain and the coupling to cellular effector systems of four somatostatin receptors (SSTR14) was studied. All four SRIF receptor subtypes were expressed in cortex and htppocampus.In addition. SSTRl mRNA was relatively abundant in the spinal cord whereas SSTRZ mRNA was also present m the striatum. The SSTR3 gene was predominantly expressed m the olfactory bulb and in the cerebellum. Conflicting results about the effector coupling of SSTRl-3 have been published prevtously. We have stably expressed human SSTRl4 in HEK 293 human embryonal kidney cells. Agomst binding to the receptor subtypes, including the recently cloned SSTR4, inhibited the formatton of forskolin-Induced CAMP. Is is concluded that, in an approprtate cellular environment. all four receptor subtypes can functionally couple to the Inhibition of adenylyl cyclase.

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“…Maximal inhibition was observed at 1 nM; half-maximal inhibition was produced by 6.3 ± 2.2 pM RC-160 and 12 ± 2 pM SMS, respectively (Fig. 5) (29). The expression of different G proteins and/or different relative amount of G proteins in transfected cell types could explain these discrepancies observed with SSTR2.…”

Section: Resultsmentioning

confidence: 91%

Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2.

Buscail

Delesque

Estève

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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The effects of s analgus RC-160and SMS-201-995 on tyrosine phosphatase and cell proliferation were investigated in COS-7 and NIH 3T3 cells expressing human somatostatin receptor subtype 1 or 2 (SSTR1 or SSTR2 antagonize the mitogenic effect of growth factors acting on tyrosine kinase receptors such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) (9-11). Furthermore, these analogues have been found to stimulate tyrosine phosphatase activity in normal and tumoral pancreatic cells (9,(12)(13)(14)(15) and to activate the dephosphorylation of EGF receptor (9, 16). The ability of somatostatin analogues to stimulate tyrosine phosphatase correlates with their inhibitory effect on pancreatic cell growth, and this correlation supports the hypothesis that the growth inhibition is mediated by dephosphorylation of tyrosine protein signals. Somatostatin analogues might suppress tumor growth by reversing the stimulatory effect of EGF on phosphorylation of EGF receptor tyrosine kinase and EGF-phosphorylated proteins (17). We also observed that a membrane tyrosine phosphatase is coeluted with somatostatin receptor, suggesting that tyrosine phosphatase may be a part ofthe signal transduction pathway promoted by somatostatin receptor occupancy (16).The somatostatin receptor subtypes and the molecular mechanism involved in the tyrosine phosphatase stimulation have been, until now, unknown (18, 19). We must better understand what physiological response every subtype elicits, how their signals are processed in the cell, and in what normal and/or pathological tissues each is expressed to choose the appropriate analogue for targeting to specific cells for therapeutic use.In the present study, we examined the effects of two somatostatin analogues, RC-160 and SMS, on binding and signal transduction pathways of the two human cloned somatostatin receptor subtypes hSSTR1 and hSSTR2 transiently expressed in COS-7 cells. We also investigated the 2315The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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The Rat SSTR2 Somatostatin Receptor Subtype Is Coupled to Inhibition of Cyclic AMP Accumulation

Cited by 39 publications

References 0 publications

The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B) differ m coupling efficiency to adenylate cyclase and in agonist‐induced receptor desensitization

The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B) differ m coupling efficiency to adenylate cyclase and in agonist‐induced receptor desensitization

Distribution and second messenger coupling of four somatostatin receptor subtypes expressed in brain

Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2.

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