Inositol trisphosphate analogues induce different oscillatory patterns in Xenopus oocytes.

Abstract

Agonists that utilize the calcium-mobilizing second messenger inositol(1,4,5)trisphosphate Ins(1,4,5)P3 usually generate oscillations in intracellular calcium. Such oscillations, based on the periodic release of calcium from the endoplasmic reticulum, can also be induced by injecting cells with Ins(1,4,5)P3. The mechanism responsible for oscillatory activity was studied in Xenopus oocytes by injecting them with different inositol trisphosphates. The plasma membrane of Xenopus oocytes has calcium-dependent chloride channels that open in response to calcium, leading to membrane depolarization. Oscillations in calcium were thus monitored by recording membrane potential. The naturally occurring Ins(1,4,5)P3 produced a large initial transient followed by a single transient or a burst of oscillations. By contrast, two analogues (Ins(2,4,5)P3 and Ins(1,4,5)P(S)3) produced a different oscillatory pattern made up of a short burst of sharp transients. Ins(1,3,4,5)P4 had no effect when injected by itself, and it also failed to modify the oscillatory responses to either Ins(2,4,5)P3 or Ins(1,4,5)P(S)3. Both analogues failed to induce a response when injected immediately after the initial Ins(1,4,5)P3-induced response, indicating that they act on the same intracellular pool of calcium. The existence of different oscillatory patterns suggests that there may be different mechanisms for setting up calcium oscillations. The Ins(2,4,5)P3 and Ins(1,4,5)P(S)3 analogues may initiate oscillations through a negative feedback mechanism whereby calcium inhibits its own release. The two-pool model is the most likely mechanism to describe the Ins(1,4,5)P3-induced oscillations.

Calcimimetic R-568 effects on activity of R990G polymorphism of calcium-sensing receptor

“…It is worth noting that the two oscillatory patterns are related to different mechanisms of activation. Transient oscillations seem to be controlled by activation of phosphoinositide pathway and are influenced by agonist concentrations and phorbol esters (PKC activators; Berridge & Potter 1990), while sinusoidal oscillations seem to result from a negative feedback loop involving inhibition of IP 3 production by PKC (Bird et al 1993). Moreover, Bird et al stated that full activation or inhibition of PKC is incompatible with sinusoidal oscillations.…”

“…5, 1, 2, and 4 mmol/l). According to Grynkiewicz et al (1985) ] i due to baseline spiking behavior (Berridge & Potter 1990). The frequency of the oscillatory phenomena was determined counting the number of oscillatory events/min.…”

Rapid kinetic measurements of 45Ca2+ mobilization reveal that Ins(2,4,5)P3 is a partial agonist at hepatic InsP3 receptors

“…Active analogues of Ins(1,4,5)P $ that are resistant to inactivation by these enzymes [4,5] are widely used and are of proven utility. Both Ins (1,4,5)PS $ (a trisphosphorothioate analogue of InsP $ ) and Ins(2,4,5)P $ have been used to distinguish the roles of InsP $ and InsP % in regulating Ca# + entry [2,[6][7][8] and to provide stable levels of InsP $ receptor activation in both intact [9][10][11] and permeabilized cells [12][13][14]. Although these analogues bind to InsP $ receptors and evoke Ca# + mobilization, they differ subtly from Ins(1,4,5)P $ in both their characteristics of binding [15] and in the patterns of Ca# + spiking they evoke [6,8,16].…”

“…Hepatocytes express type II (81 %) and type I (19 %) Ins(1,4,5)P $ receptors [28], but the lesser effect of Ins(2,4,5)P $ is unlikely to reflect a selective interaction with particular subtypes. Firstly, in hepatocytes, Ins (2,4,5) [6,8,16], an effect which is not attributable to their different susceptibilities to phosphorylation. Furthermore, whereas prior injection of Ins(1,4,5)P $ prevented a subsequent response to Ins(2,4,5)P $ , the converse was not true [6].…”

Ca2+ inhibition of inositol trisphosphate‐induced Ca2+ release in single smooth muscle cells of guinea‐pig small intestine.

“…Some other models assume a more steady level of InsP3 during phospholipase C activation and different types of positive and/or negative feedback control of some part of the Ca2+-release process to explain the [Ca2+] Petersen, 1990). On the other hand, Ca2+-dependent inhibition of the InsP3-gated Ca2+-release channel (InsP3 receptor) (Worley, Baraban, Supattapone, Wilson & Snyder, 1987;Joseph, Rice & Williamson, 1989;Berridge & Potter, 1990; Jino, 1990;Parker & Ivorra, 1990;Zhao & Muallem, 1990;Bezprozvanny, Watras & Ehrlich, 1991;Finch, Turner & Goldin, 1991;Fohr, Ahnert-Hilger, Stecher, Scott & Gratzl, 1991;Keizer & De Young, 1992;Zhang & Muallem, 1992;Levy & Payne, 1993) can also play an important role as a negative feedback control in giving rise to the Ca2+ oscillations.…”