Regulation of inositol trisphosphate accumulation by muscarinic cholinergic and H1-histamine receptors on human astrocytoma cells. Differential induction of desensitization by agonists

Abstract

Although activation of muscarinic cholinergic receptors on 1321N1 human astrocytoma cells results in a linear accumulation of inositol phosphates for up to 60 min in the presence of LiCl [Masters, Quinn & Brown (1985) Mol. Pharmacol. 27, 325-332], activation of H1-histamine receptors resulted in an increase in total inositol phosphate formation that was maintained for less than 5 min. The effects of stimulation of these two receptors on accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] were also examined. Incubation of 1321N1 cells with carbachol resulted in a rapid accumulation of all three inositol phosphates, reaching a maximum within 30 s; this elevated value was maintained for up to 60 min. The rate of disappearance of Ins(1,3,4)P3 from carbachol-treated cells after the addition of atropine paralleled or exceeded the rate of disappearance of Ins(1,4,5)P3. Although the initial rates of accumulation of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1,3,4,5)P4 in the presence of histamine were similar to that observed with carbachol, the amounts of these inositol phosphates had returned to control values within 5 min after the addition of histamine. The results indicate that, although the acute effects of muscarinic receptor and H1-histamine receptor stimulation on phosphoinositide hydrolysis are very similar, the histamine receptor is desensitized rapidly, whereas the muscarinic receptor is not. This effect on histamine-receptor function is apparently homologous, since preincubation of 1321N1 cells with histamine did not decrease the subsequent response to carbachol.

Muscarinic Receptors Mediate Phospholipase C-dependent Activation of Protein Kinase B via Ca2+, ErbB3, and Phosphoinositide 3-Kinase in 1321N1 Astrocytoma Cells

“…The smaller effects of these stimuli on PKB activity compared with that of carbachol are generally compatible with their relative impacts on PLC activity over the time scale shown. Direct, quantitative comparison of these events is difficult, however, because muscarinic receptor stimulation induces persistent activation of PLC in 1321N1 cells, whereas PLC responses to the other stimuli vary both in initial magnitude and in the rate and extent of desensitization (22,29,31). Indeed the comparative efficacy of carbachol and SFLLRN in activating PKB is particularly noteworthy, because the initial (Յ30-s) PLC response to the latter is severalfold greater than that elicited by the former ligand but desensitizes extensively within 1-2 min after agonist addition (22), during which phase neither carbachol nor SFLLRN activates PKB.…”

“…These include histamine H 1 receptors (29, 30), protease-activated receptors sensitive to thrombin (31), and the synthetic peptide ligand SFLLRN (22) and bradykinin receptors (see Fig. 4).…”

Different profiles of desensitization dynamics in guinea‐pig jejunal longitudinal smooth muscle after stimulation with histamine and methacholine

“…It has been shown that histamine responses can be modulated in vivo (Manning et al, 1987) and in vitro. Histamine-induced desensitization of the H1-receptor has been documented in various isolated cell systems (Lewis Baenzinger et al, 1981;Brown et al, 1986;Nakahata & Harden, 1987;McDonough et al, 1988) and smooth muscle preparations (Anderson et al, 1979;Kenakin & Cook, 1979;Bielkiewicz & Cook, 1984;Hishinuma & Uchida, 1988).…”

Calcium mobilization and response recovery following P2‐purinoceptor stimulation of rat isolated alveolar type II cells

“…ATP stimulation of hepatocytes and Ehrlich ascites tumour cells leads to cytosolic elevation of 1P3 (Charest et al, 1985;Dubyak, 1986), and treatment of permeabilized cells with IP3 mobilizes Ca2+ from intracellular stores (Joseph et al, 1984;Dubyak, 1986). Although production of IP3 continues in the presence of bound agonist (Ambler et al, 1987;Nakahata & Harden, 1987), the transient nature of the Ca2+ peak results from the combined effect of Ca2 + extrusion by plasma membrane, Ca2, Mg2 +-dependent ATPase, uptake by other cytoplasmic constituents, and Ca2+ pool depletion (Putney, 1986;Merritt & Rink, 1987).…”