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Biomedical subjects

J E Merritt

Publications and source records attributed to J E Merritt.

51 records · Page 3Linked to original sources
PubMed1986

A guanine nucleotide-dependent regulatory protein couples substance P receptors to phospholipase C in rat parotid gland.

Electrically permeabilized cells of rat parotid gland, prelabelled with [3H]-inositol, synthesized [3H]-inositol phosphates (IP3 and IP2) when stimulated with alpha 1-adrenergic, muscarinic-cholinergic, and substance P receptor-agonists. Non-hydrolyzable analogues of GTP (GTP gamma S and GppNHp) also stimulated [3H]-IP3 formation by permeabilized cells and they potentiated the stimulation by receptor-agonists. These effects of guanine nucleotides occurred only with GTP analogues and only in permeabilized cells indicating an intracellular site of action. NaF stimulated [3H]-IP3 accumulation, an effect that was not entirely attributable to the ability of F- to inhibit (1,4,5)IP3 degradation. These results suggest that a guanine nucleotide-dependent regulatory protein couples Ca2+-mobilizing receptors to phospholipase C in parotid gland.

Animals↗
PubMed1986

Formation and biological action of inositol 1,4,5-trisphosphate.

A wide variety of receptors appear to be coupled to a phospholipase C (EC 3.1.4.3) that hydrolyzes inositol lipids. This reaction is believed to provide a link between receptor activation and cellular Ca2+ mobilization. The mechanisms by which this occurs are believed to involve inositol 1,4,5-trisphosphate (1,4,5-IP3), which signals release of Ca2+ from the endoplasmic reticulum. In rat parotid acinar cells made permeable with saponin, 1,4,5-IP3 induced rapid release of sequestered Ca2+. In intact parotid cells, the concentration-response relationship for methacholine-induced IP3 formation was similar to the relationship for muscarinic receptor occupancy by methacholine. About 10-fold lower concentrations of methacholine were sufficient to increase cytosolic [Ca2+] and to activate secretion, indicating an excess IP3 forming capacity for the muscarinic receptor. The mechanisms for the coupling of receptors to IP3 formation were studied in pancreatic acinar cells made permeable electrically. In this preparation, nonhydrolyzable derivatives of GTP potentiated agonist-induced IP3 production, which suggests the involvement of a guanine nucleotide-dependent regulatory protein. The effects of agonists and guanine nucleotides were not altered by pretreating the acinar cells with cholera or pertussis toxins, which indicated that the regulatory protein linking receptors to IP3 formation is distinct from the ones involved in the regulation of adenylate cyclase.

Animals↗
PubMed1985

Pancreatic amylase secretion and cytoplasmic free calcium. Effects of ionomycin, phorbol dibutyrate and diacylglycerols alone and in combination.

Both protein kinase C and Ca2+ may act in concert to bring about activation of secretion. This study examined the actions on pancreatic acini of ionomycin and phorbol dibutyrate, which selectively stimulate one or the other of these pathways; their stimulatory effects were compared with those of receptor agonists, such as carbachol and caerulein, which activate phospholipase C. The Ca2+ ionophore ionomycin produced a dose-dependent increase in amylase secretion and intracellular free Ca2+ (as measured by quin-2). The increase in amylase secretion elicited by carbachol or caerulein was accompanied by a small sustained increase in intracellular free Ca2+, following an initial peak. However, the elevation in intracellular free Ca2+ produced by these receptor agonists for a given level of amylase secretion was less than that observed with ionomycin. Phorbol dibutyrate stimulated amylase secretion by a mechanism that was independent of extracellular Ca2+, and no change in intracellular free Ca2+ was observed. Synergistic stimulatory effects of phorbol dibutyrate and ionomycin were observed, whether the phorbol ester was present before, or in combination with, ionomycin. Diacylglycerols containing unsaturated fatty acids (1,2-dioleoylglycerol and 1,3-dioleoylglycerol) also stimulated amylase secretion and exhibited synergistic effects on secretion with ionomycin. These findings suggest that complete activation of amylase secretion from the pancreas requires stimulation of both Ca2+-dependent and protein kinase C-activated pathways.

Amylases↗
PubMed1984

The possible involvement of both calcium and cyclic AMP in the dopaminergic inhibition of prolactin secretion.

Dopamine inhibited basal, TRH-, IBMX- and A23187-stimulated prolactin secretion from rat anterior pituitary cells. However, dopamine did not inhibit prolactin secretion stimulated by elevated K+ concentrations. These data are interpreted in terms of dopaminergic inhibition of both cyclic AMP production and Ca2+ influx through agonist-, but not voltage-, dependent Ca2+ channels.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Studies on the involvement of calcium and calmodulin in the action of growth-hormone-releasing factor.

A possible role for Ca2+ and calmodulin in the action of growth-hormone-releasing factor (GHRF) was investigated. Low extracellular Ca2+ (less than 100 microM), methoxyverapamil, flunarizine, cinnarizine, and Co2+ decreased both basal and GHRF-stimulated growth-hormone secretion, but did not totally inhibit GHRF-stimulated secretion. A calmodulin antagonist, W7, abolished GHRF-stimulated GH secretion, with no effect on basal secretion. It is suggested that GHRF may act primarily by elevating cellular cyclic AMP, which may then modulate calcium mobilization or flux; the increased intracellular Ca2+ concentrations may then activate calmodulin.

Animals↗
PubMed1984

Dual effects of manganese on prolactin secretion.

The effect of Mn2+ (a commonly used Ca2+ antagonist) on prolactin secretion from pituitary cells was investigated. In the presence of normal extracellular Ca2+ levels (2.5mM), Mn2+ inhibited basal, TRH- and K+- stimulated prolactin secretion. The Ca2+ ionophore, A23187, partially overcame the inhibitory effect of Mn2+. However, in the presence of low extracellular Ca2+ (less than 100 microM), which decreased basal prolactin secretion and abolished any stimulatory effects of TRH or K+, a paradoxical stimulatory effect was observed with Mn2+ in the presence of A23187. In the presence of Ca2+, Mn2+ appeared to be inhibitory due to its Ca2+ antagonistic effects, but at low Ca2+ levels, intracellular stimulatory effects of Mn2+ became apparent.

Animals↗
PubMed1984

Flunarizine, a calcium influx blocker, inhibits TRH-but not potassium-stimulated prolactin secretion.

The effect of flunarizine on the secretion of prolactin from monolayer cultures of normal rat pituitary cells has been determined. Both basal and TRH-stimulated secretion were found to be significantly inhibited by micromolar concentrations of flunarizine, whereas depolarization (high K+)-stimulated secretion was virtually unaffected. These results indicate that TRH-stimulated prolactin secretion probably involves calcium influx and that flunarizine may be useful as a probe for particular Ca2+ channels.

Animals↗
PubMed1984

An investigation of the involvement of calcium in the control of prolactin secretion: studies with low calcium, methoxyverapamil, cobalt and manganese.

The possible role of calcium as a primary mediator in the control of prolactin secretion from normal pituitary cells was examined. Basal prolactin secretion, and secretion stimulated by thyrotrophin releasing hormone (TRH), raised K+ or the calcium ionophore, A23187, were all dependent on the presence of extracellular Ca2+. The calcium channel antagonists, methoxyverapamil, cobalt and manganese, inhibited basal, TRH- and K+-stimulated prolactin secretion. In addition, prolactin secretion stimulated by a phosphodiesterase inhibitor, isobutylmethylxanthine, which increases cellular cyclic AMP, was inhibited by these Ca2+ antagonists. These observations indicate that Ca2+ may be the primary intracellular mediator in the control of prolactin secretion, with cyclic AMP having a secondary modulatory role on Ca2+ influx, probably on voltage-dependent Ca2+ channels.

Animals↗
PubMed1983

The possible role of calmodulin in the inhibition of prolactin secretion by dopaminergic antagonists.

Several previous reports have indicated that a number of dopaminergic antagonists paradoxically inhibit prolactin secretion at micromolar concentrations. It is well known that some of these drugs, including pimozide and the phenothiazines, are inhibitors of calmodulin activity. Here we report that micromolar concentrations of several dopaminergic antagonists inhibit prolactin secretion from isolated rat anterior pituitary cells and calmodulin activity (calmodulin-activated cyclic GMP phosphodiesterase). Inhibition of calmodulin activity may thus, at least partially, explain the inhibitory effect of these drugs on prolactin secretion.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1983

The relationship between prolactin secretion and calmodulin activity.

The possible role of calmodulin in the control of prolactin secretion was examined. The effects of a wide variety of agents on inhibition of prolactin secretion from isolated rat anterior pituitary cells and inhibition of calmodulin activity in an in-vitro system (calmodulin-activated cyclic GMP phosphodiesterase) were compared. A number of phenothiazines showed a close correlation of potencies in the two systems, as did the more specific calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W7), suggesting that calmodulin may be involved in the control of prolactin secretion. Some other drugs also inhibited both prolactin secretion and calmodulin activity in addition to their other well-characterized biochemical effects. However, many of these drugs (including two phenothiazines) were more potent inhibitors of prolactin secretion than of calmodulin activity, suggesting that other intracellular systems in addition to calmodulin may be involved in the control of the secretory process.

Animals↗