Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates.
Standard
Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates. / DeLisle, S; Radenberg, T; Wintermantel, M R; Tietz, C; Parys, J B; Pittet, D; Welsh, M J; Mayr, Georg W.
In: AM J PHYSIOL-HEART C, Vol. 266(2 Pt 1), 1994, p. 429-436.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates.
AU - DeLisle, S
AU - Radenberg, T
AU - Wintermantel, M R
AU - Tietz, C
AU - Parys, J B
AU - Pittet, D
AU - Welsh, M J
AU - Mayr, Georg W.
PY - 1994
Y1 - 1994
N2 - To further understand how the second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] interacts with its intracellular receptor, we injected 47 highly purified inositol phosphate (InsP) positional isomers in Xenopus oocytes and compared their potency in releasing intracellular Ca2+. The potency of the Ca(2+)-releasing InsPs spanned four orders of magnitude. Seven compounds, including the novel inositol 1,2,4,5-tetrakisphosphate [D/L-Ins (1,2,4,5)P4] and D/L-Ins(1,4,6)P3, had a very high potency. All of these highly active InsPs shared the following structure: two D-trans-equatorial phosphates (eq-P) and one equatorial hydroxyl (eq-OH) attached to ring carbons D-4, D-5, and D-6 (or to the structurally equivalent D-1, D-6, and D-5 carbons). This permissive structure was not sufficient for Ca2+ release, because it was also found in two inactive compounds, Ins(1,6)P2 and Ins(1,3,6)P3. To be active, InsPs also required the structural equivalent of a D-3 eq-OH and/or a D-1 eq-P. Together, our data reveal how the structure of the InsP molecule affects its ability to release Ca2+.
AB - To further understand how the second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] interacts with its intracellular receptor, we injected 47 highly purified inositol phosphate (InsP) positional isomers in Xenopus oocytes and compared their potency in releasing intracellular Ca2+. The potency of the Ca(2+)-releasing InsPs spanned four orders of magnitude. Seven compounds, including the novel inositol 1,2,4,5-tetrakisphosphate [D/L-Ins (1,2,4,5)P4] and D/L-Ins(1,4,6)P3, had a very high potency. All of these highly active InsPs shared the following structure: two D-trans-equatorial phosphates (eq-P) and one equatorial hydroxyl (eq-OH) attached to ring carbons D-4, D-5, and D-6 (or to the structurally equivalent D-1, D-6, and D-5 carbons). This permissive structure was not sufficient for Ca2+ release, because it was also found in two inactive compounds, Ins(1,6)P2 and Ins(1,3,6)P3. To be active, InsPs also required the structural equivalent of a D-3 eq-OH and/or a D-1 eq-P. Together, our data reveal how the structure of the InsP molecule affects its ability to release Ca2+.
M3 - SCORING: Zeitschriftenaufsatz
VL - 266(2 Pt 1)
SP - 429
EP - 436
JO - AM J PHYSIOL-HEART C
JF - AM J PHYSIOL-HEART C
SN - 0363-6135
ER -
