Changes in Inositol 1,4,5‐Trisphosphate and Inositol 1,3,4,5‐Tetrakisphosphate Mass Accumulations in Cultured Adrenal Chromaffin Cells in Response to Bradykinin and Histamine

Abstract

In previous studies it has been shown that both bradykinin and histamine increase the formation of 3H-labeled inositol phosphates in adrenal chromaffin cells prelabelled with [3H]inositol and that both these agonists stimulate release of catecholamines by a mechanism dependent on extracellular calcium. Here, we have used mass assays of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] to investigate changes in levels of these two candidates as second messengers in response to stimulation with bradykinin and histamine. Bradykinin increased the mass of Ins(1,3,4,5)P4 despite the failure in earlier studies with [3H]inositol-labelled cells to observe a bradykinin-mediated increase in content of [3H]InsP4. Bradykinin elicited a very rapid increase in level of Ins(1,4,5)P3, which was maximal at 5-10 s and then rapidly decreased to a small but sustained elevation at 2 min. The bradykinin-elicited Ins(1,3,4,5)P4 response increased to a maximum at 30-60 s and at 2 min was still elevated severalfold above basal levels. Histamine, which produced a larger overall total inositol phosphate response in [3H]inositol-loaded cells, produced significantly smaller Ins(1,4,5)P3 and Ins(1,3,4,5)P4 responses compared with bradykinin. The bradykinin stimulation of Ins(1,4,5)P3 accumulation was partially dependent on a high (1.8 mM) extracellular Ca2+ concentration, whereas the Ins(1,3,4,5)P4 response was almost completely lost when the extracellular Ca2+ concentration was reduced to 100 nM. Changes in the inositol polyphosphate second messengers are compared with the time course of bradykinin-stimulated increases in free intracellular Ca2+ concentrations and noradrenaline release.

GABAB receptors modulate catecholamine secretion in chromaffin cells by a mechanism involving cyclic AMP formation

“…These include muscarinic cholinoceptors (Cheek & Burgoyne, 1985), opioid peptide (Lemaire et al, 1981), substance P (Livett et al, 1979), bradykinin (Owen et al, 1989), histamine HI (Chaliss et al, 1991), dopamine DI and D2 (Stauderman & Pruss, 1990;Huettl et al, 1991), prostaglandin E2 (Negishi et al, 1989;Ito et al, 1991), adenosine (Chern et al, 1988), angiotensin II (Marley et al, 1989;O'Sullivan & Burgoyne, 1989) and GABAA receptors (Castro et al, 1989).…”

Inhibitory Effects of Olmesartan on Catecholamine Secretion from the Perfused Rat Adrenal Medulla

“…In supporting this finding, it has been shown that cyclopiazonic acid easily penetrates into the cytoplasm through the plasma membrane and reduces Ca 2＋ -ATPase activity in sarcoplasmic/endoplasmic reticulum, resulting in increase in the subsequent Ca 2＋ release from those storage sites and thereby increase of Ca 2＋ -dependent K ＋ -current [38]. Moreover, in bovine adrenal chromaffin cells, stimulation of muscarinic ACh receptors is also proposed to cause activation of phosphoinositide metabolism, resulting in the formation of inositol 1,4,5-trisphosphate, which induces the mobilization of Ca 2＋ from the intracellular pools [35,39]. However, in the present study, it is uncertain whether the inhibitory effect of the olmesartan on Ca 2＋ movement from intracellular pools is due to their direct effect on the PI response or the indirect effect as a result of AT1 receptor blockade by olmesartan.…”

Effects of Losartan on Catecholamine Release in the Isolated Rat Adrenal Gland

“…In supporting this finding, it has been shown that cyclopiazonic acid easily penetrates into the cytoplasm through the plasma membrane and reduces Ca 2＋ -ATPase activity in sarcoplasmic/endoplasmic reticulum, resulting in increase in the subsequent Ca 2＋ release from those storage sites and thereby increase of Ca 2＋ -dependent K ＋ -current (Suzuki et al, 1992). Moreover, in bovine adrenal chromaffin cells, stimulation of muscarinic ACh receptors is also proposed to cause activation of phosphoinositide metabolism, resulting in the formation of inositol 1,4,5-trisphosphate, which induces the mobilization of Ca 2＋ from the intracellular pools (Cheek et al, 1989;Challiss et al, 1991). However, in the present study, it is uncertain whether the inhibitory effect of the losartan on Ca 2＋ movement from intracellular pools is due to their direct effect on the PI response or the indirect effect as a result of AT1 receptor blockade by losartan.…”