Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-5-14
pubmed:abstractText
1. The mouse corticotroph tumour cell line AtT-20 is a useful model to investigate the physiological role of native somatostatin (SRIF, Somatotropin release inhibitory factor) receptor subtypes (sst(1) - sst(5)). The objective of this study was to characterise the pharmacological features and the functional effects of SRIF receptors expressed by AtT-20 cells using radioligand binding and cAMP accumulation. 2. [(125)I]LTT-SRIF-28, [(125)I]CGP 23996, [(125)I]Tyr(10)-cortistatin-14 and [(125)I]Tyr(3)-octreotide labelled SRIF receptor binding sites with high affinity and in a saturable manner (B(max)=315, 274, 239 and 206 fmol mg(-1), respectively). [(125)I]LTT-SRIF-28 labels significantly more sites than [(125)I]Tyr(10) -cortistatin-14 and [(125)I]Tyr(3) -octreotide as seen previously in cells expressing pure populations of sst(2) or sst(5) receptors. 3. SRIF analogues displaced the binding of the four radioligands. sst(2/5) receptor-selective ligands showed much higher affinity than sst(1/3/4) receptor-selective ligands. The binding profile of [(125)I]Tyr(3)-octreotide was different from that of [(125)I]LTT-SRIF-28, [(125)I]CGP 23996 and [(125)I]Tyr(10)-cortistatin-14. The sst(5/1) receptor-selective ligand L-817,818 identified two binding sites, one with subnanomolar affinity (sst(5) receptors) and one with micromolar affinity (sst(2) receptors); however, the proportions were different: 70 - 80% high affinity with [(125)I]LTT-SRIF-28, [(125)I]CGP 23996, [(125)I]Tyr(10)-cortistatin-14, but only 20% with [(125)I]Tyr(3)-octreotide. 4. SRIF analogues inhibited the forskolin-stimulated cAMP levels depending on concentration. sst(2/5) receptor-selective ligands were highly potent, whereas sst(1/3/4) receptor-selective ligands had no significant effects. The sst(2) receptor antagonist D-Tyr(8)-CYN 154806 competitively antagonised the effects of SRIF-14 and sst(2) receptor-preferring agonists, but not those of L-817,818. 5. The complex binding properties of SRIF receptor analogues indicate that sst(2) and sst(5) receptors are the predominant SRIF receptors expressed on AtT-20 cell membranes with no or only negligible presence of sst(1), sst(3) and sst(4) receptors. In the functional studies using cAMP accumulation, only sst(2) and sst(5) receptors appear to play a role. However, the "predominant" receptor appears to be the sst(2) receptor, although sst(5) receptors can also mediate the effect, when the ligand is not able to activate sst(2) receptors. This clearly adds flexibility to SRIF-mediated functional effects and suggests that the physiological role of SRIF and its analogues may be mediated preferentially via one subtype over another.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10024356, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10219983, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10383439, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10433861, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10598788, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10711345, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10713101, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10753124, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-10818261, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11134004, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11520208, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11591512, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11858797, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11880655, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11882916, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11896051, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11897118, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-11931345, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-12065886, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-12169771, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-12595949, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-12616335, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-12668053, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-1349280, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-1967144, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-2895889, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-7649075, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-7733906, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-7781707, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-7804834, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-7904601, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-8684611, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-8809804, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9029503, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9050007, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9145917, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9187273, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-942051, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9421441, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9593843, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9784130, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9822540, http://linkedlifedata.com/resource/pubmed/commentcorrection/12746229-9888991
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0007-1188
pubmed:author
pubmed:issnType
Print
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-21
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Pharmacological characterisation of native somatostatin receptors in AtT-20 mouse tumour corticotrophs.
pubmed:affiliation
Dipartimento di Fisiologia e Biochimica G. Moruzzi, Università di Pisa, 56127 Pisa, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't