Rapid increases in inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and cytosolic free Ca2+ in agonist-stimulated pancreatic acini of the rat. Effect of carbachol, caerulein and secretin

Abstract

We compared the time course of increases in isomers of inositol trisphosphate [Ins(1,4,5)P3] and Ins(1,3,4)P3] and the tetrakisphosphate [Ins(1,3,4,5)P4] with changes in cytosolic free Ca2+ [( Ca2+]i) in dispersed pancreatic acini of the rat. There were rapid (5s) increases in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 in response to carbachol, caerulein and secretin, whereas Ins(1,3,4)P3 increased more slowly. All three secretagogues induced increases in [Ca2+]i, which reached a peak at 15-20 s. Our results indicate that the very rapid formation of Ins(1,4,5)P3 is compatible with its second-messenger role in the initial elevation of [Ca2+]i.

Inositol 1,3,4,5-tetrakisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused mouse lacrimal acinar cells

“…5) (compare also Irvine & Moor, 1986). It is therefore clear that Ins 1,3,4,5 P4, which is rapidly formed from Ins 1,4,5 P3 during receptor activation (Batty, Nahorski & Irvine, 1985;Hawkins, Stephens &Downes, 1986;Trimble et al, 1987), has a dramatic effect on cellular Ca 2+ handling since it transforms the transient Ca2+-activated K + current response evoked by Ins 1,4,5 P3 alone into a long sustained current increase (Fig. 1).…”

Molecular basis for the integration of inositol phosphate signaling pathways via human ITPK1

“…In support of this idea, we have shown that alkalinization of insulin granules by Ins(3,4,5,6) P 4 has the effect of reducing insulin secretion from pancreatic β-cells (Renström et al, 2002). This has previously led us (Renström et al, 2002) to consider what might be the pathological consequences of a persistently activated pancreatic Ins(3,4,5,6) P 4 signal, such as that which would inevitably (see Section 4) accompany sustained glucose-dependent activation of PLC (Trimble et al, 1987). Perhaps in some individuals, such abnormally elevated Ins(3,4,5,6) P 4 levels contribute to the hyperglycemia-dependent refractoriness of β-cells (Meyer et al, 2002) which typifies type 2 diabetes etiology (Kilpatrick and Robertson, 1998).…”

Sustained Changes in Acetylcholine and Amino Acid Contents of Brain Regions Following Microsphere Embolism in Rats

“…These results suggest that the effect of isoprenaline on DAG formation is mediated by a,-adrenoceptor activation, that it is not related to the increase in cyclic AMP, and that it is closely related to PIP2 hydrolysis. Various agonists cause phospholipase C-dependent phosphoinositide hydrolysis through the receptor-G pro tein system and stimulate the release of two putative sec ond messengers, inositol 1,4,5-phosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG) (1)(2)(3)(4)(5). DAG may activate a protein kinase C and thus play an important role in the process leading to exocytosis (6).…”