Vasoactive intestinal polypeptide stimulation of protein secretion from rat lacrimal gland acini

1984 ◽  
Vol 247 (5) ◽  
pp. G502-G509 ◽  
Author(s):  
D. A. Dartt ◽  
A. K. Baker ◽  
C. Vaillant ◽  
P. E. Rose
Keyword(s):  
Protein Secretion ◽  
Vasoactive Intestinal Polypeptide ◽  
Lacrimal Gland ◽  
Maximum Concentration ◽  
Nerve Fibers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Camp Content ◽  
Cholinergic Antagonist ◽  
Intestinal Polypeptide

The effect of vasoactive intestinal polypeptide (VIP) on protein secretion from lacrimal gland was investigated by using acini prepared by collagenase digestion of rat exorbital lacrimal glands. Protein secretion was determined by incubating the acini for 0-40 min and analyzing the supernatant for peroxidase, a protein secreted by the rat exorbital lacrimal gland. VIP (10(-10) to 10(-7) M) stimulated secretion in a concentration-dependent manner. A maximum concentration of VIP (10(-8) M) stimulated secretion to the same extent as a maximum concentration of carbachol (10(-5) M). The cholinergic antagonist atropine at a concentration (10(-5) M) that completely abolished carbachol-induced secretion did not alter VIP-stimulated secretion. The secretory effects of maximal concentrations of VIP and carbachol were additive, but decreasing the carbachol concentration potentiated secretion. Unlike carbachol, which had no effect on the acinar cAMP level, VIP increased cAMP content sixfold. Immunohistochemical staining demonstrated VIP-like immunoreactivity in nerve fibers throughout the gland, distributed primarily around acini. We conclude that VIP-like immunoreactive nerves are present in the lacrimal gland and that VIP can stimulate protein secretion but utilizes a pathway separate from, but convergent with, that used by cholinergic agonists.

Antagonists of epithelial chloride channels inhibit cAMP synthesis

1991 ◽  
Vol 69 (4) ◽  
pp. 501-506 ◽  
Author(s):  
S. Heisler
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Chloride Channels ◽  
Chloride Transport ◽  
Chloride Secretion ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Camp Synthesis ◽  
Camp Formation ◽  
Intestinal Polypeptide

In past studies we observed that the chloride channel blocker, diphenylamine-2-carboxylate (DPC) and chemically related drugs (Hoechst compounds 131, 143, 144) inhibited cAMP formation in mouse pituitary tumor cells. The object of this study was to determine whether these drugs inhibited chloride transport in human T-84 colonic carcinoma cells through an effect on cAMP metabolism. Chloride secretion (measured as 125I efflux from isotope-preloaded cells) was stimulated in a concentration-dependent manner by vasoactive intestinal polypeptide (VIP) (EC50 = 1.5 × 10−10 M) which similarly increased cAMP synthesis (EC50 = 1.6 × 10−8 M). The cAMP response to VIP was inhibited 17, 52, 55, and 78% maximally by DPC and compounds 144, 143, and 131, respectively. In untreated T-84 cells, 125I secretion fell by 66% after 3 min; VIP (10−7 M) increased secretion about fivefold over the same period. Both basal and VIP-stimulated 125I secretion were inhibited up to 60% by compound 131. Pretreatment of cells with pertussis toxin did not attenuate the inhibitory effect of channel blockers on either VIP-stimulated cAMP synthesis or 125I secretion. The cationophore, A-23187, which had no effect on cAMP formation, and 8-Br-cAMP both stimulated 125I secretion from T-84 cells. These secretory responses were inhibited by compound 131. The mechanism by which phenylanthranilic acids antagonize cAMP synthesis and its significance is not known; however, the data suggest that this family of drugs may inhibit chloride transport by both cAMP-dependent and independent mechanisms.Key words: T-84 cells, chloride secretion, vasoactive intestinal polypeptide, diphenylamine-2-carboxylate, inhibition of cyclic AMP synthesis.

α1-Adrenergic and cholinergic agonists activate MAPK by separate mechanisms to inhibit secretion in lacrimal gland

2003 ◽  
Vol 284 (1) ◽  
pp. C168-C178 ◽  
Author(s):  
Isao Ota ◽  
Driss Zoukhri ◽  
Robin R. Hodges ◽  
José D. Rios ◽  
Vanja Tepavcevic ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Lacrimal Gland ◽  
Egf Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Signaling Mechanisms ◽  
Mitogen Activated Protein ◽  
Secretion Inhibition

The purpose of this study was to determine the role of p42/p44 mitogen-activated protein kinase (MAPK) in α1-adrenergically and cholinergically stimulated protein secretion in rat lacrimal gland acinar cells and the pathways used by these agonists to activate MAPK. Acini were isolated by collagenase digestion and incubated with the α1-adrenergic agonist phenylephrine or the cholinergic agonist carbachol, and activation of MAPK and protein secretion were then measured. Phenylephrine and carbachol activated MAPK in a time- and concentration-dependent manner. Inhibition of MAPK significantly increased phenylephrine- and carbachol-induced protein secretion. Inhibition of EGF receptor (EGFR) with AG1478, an inhibitor of the EGFR tyrosine kinase activity, significantly increased phenylephrine- but not carbachol-induced protein secretion. Whereas phenylephrine-induced activation of MAPK was completely inhibited by AG1478, activation of MAPK by carbachol was not. Phenylephrine stimulated tyrosine phosphorylation of the EGFR, whereas carbachol stimulated p60Src, and possibly Pyk2, to activate MAPK. We conclude that, in the lacrimal gland, activation of MAPK plays an inhibitory role in α1-adrenergically and cholinergically stimulated protein secretion and that these agonists use different signaling mechanisms to activate MAPK.

Alpha 1-adrenergic and cholinergic agonists use separate signal transduction pathways in lacrimal gland

1992 ◽  
Vol 262 (6) ◽  
pp. G1087-G1096 ◽  
Author(s):  
R. R. Hodges ◽  
D. M. Dicker ◽  
P. E. Rose ◽  
D. A. Dartt
Keyword(s):  
Protein Secretion ◽  
Lacrimal Gland ◽  
Inositol Phosphates ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cholinergic Agonists ◽  
Substrate Protein ◽  
Camp Levels

The cellular transduction pathways used by alpha 1-adrenergic and cholinergic agonists were compared in isolated acini from rat exorbital lacrimal glands. Peroxidase secretion was the index of protein secretion. Inositol phosphates were measured by anion exchange chromatography, intracellular free Ca2+ concentration ([Ca2+]i) by fluorescence methods using fura-2, cellular adenosine 3',5'-cyclic monophosphate (cAMP) levels by protein binding radioassay, and protein kinase C (PKC) activity by [32P]ATP incorporation into exogenous substrate. Protein secretion stimulated by simultaneous addition of the alpha 1-adrenergic agonist phenylephrine and the cholinergic agonist carbachol was additive. Carbachol (10(-3) M) significantly increased the ratios of inositol phosphates to inositol during a 1- or 20-min incubation in contrast to phenylephrine (10(-5) to 10(-2) M), which did not. Phenylephrine (10(-3) M) significantly increased the [Ca2+]i by a maximum of 15 +/- 3 nM compared with carbachol (10(-4) M), which increased [Ca2+]i to a maximum of 90 +/- 14 nM. Phenylephrine (10(-4) M) did not increase cAMP levels. Phenylephrine (10(-5) to 10(-3) M) decreased cytosolic PKC activity in a concentration-dependent manner. Carbachol (10(-3) M) transiently caused a slight decrease in cytosolic PKC activity. Our results indicate that alpha 1-adrenergic and cholinergic agonists use separate and different pathways to stimulate the lacrimal gland.

scholarly journals Phospholipase D1, but Not D2, Regulates Protein Secretion Via Rho/ROCK in a Ras/Raf-Independent, MEK-Dependent Manner in Rat Lacrimal Gland

2011 ◽  
Vol 52 (5) ◽  
pp. 2199 ◽  
Author(s):  
Robin R. Hodges ◽  
Erin Guilbert ◽  
Marie A. Shatos ◽  
Viswanathan Natarajan ◽  
Darlene A. Dartt
Keyword(s):  
Protein Secretion ◽  
Lacrimal Gland ◽  
Dependent Manner ◽  
Phospholipase D1

Riluzole Anesthesia

1996 ◽  
Vol 85 (3) ◽  
pp. 626-634. ◽  
Author(s):  
M. Bruce MacIver ◽  
Shanti M. Amagasu ◽  
Anthony A. Mikulec ◽  
Frances A. Monroe
Keyword(s):  
Butyric Acid ◽  
Brain Slices ◽  
Nerve Fibers ◽  
Dependent Manner ◽  
Gamma Amino Butyric Acid ◽  
General Anesthetic ◽  
Output Analysis ◽  
Concentration Dependent Manner ◽  
Paired Pulse ◽  
Amino Butyric Acid

Background Riluzole (RP 54274) is an experimental benzothiazole with anesthetic properties, but little is known about its synaptic or cellular actions. Methods The authors investigated riluzole effects on synaptic response of CA 1 pyramidal neurons in rat hippocampal brain slices. Electrophysiologic recordings of population spikes (PS), excitatory postsynaptic potentials (EPSP), and fiber volleys were studied. Paired pulse stimulation (120 ms interpulse interval) was used to measure effects on gamma-amino butyric acid (GABA)-mediated synaptic inhibition, and stimulus trains (33 Hz) were used to test for use-dependent effects. Results Synaptically evoked PS discharge was blocked in a concentration-dependent manner by riluzole (2.0-20 microM), similar to effects produced by other anesthetics. Paired pulse inhibition was not altered by riluzole. In contrast, 20 microM thiopental produced a marked increase in paired pulse inhibition. Riluzole (5.0 microM) produced a 46.6 +/- 19.8% depression of glutamate-mediated EPSPs, which could account for most of the mate-mediated EPSPs, which could account for most of the depression of PS discharge (54.2 +/- 12.6%) produced by this concentration. Riluzole produced a 36 +/- 17% depression of fiver volley amplitudes, which, based on input/output analysis, could completely account for the depression of EPSPs. The depression of fiber volley amplitudes showed a marked use-dependence; the second and subsequent action potentials in a train were progressively depressed by riluzole to a greater extent than the first action potential. Conclusions Riluzole produced a potent block of excitatory synaptic transmission via depression of presynaptic conduction in glutamatergic nerve fibers. The use-dependent depression observed resembled that produced by some local anesthetics on nerve conduction and sodium channels. The presynaptic action, together with a lack of effect on gamma-amino butyric acid-mediated inhibition, provides a unique mechanism of action for a general anesthetic.

scholarly journals A Light and Electron Microscopic Immunohistochemical Study of Vasoactive Intestinal Polypeptide— And Substance P-Containing Nerve Fibers along the Cerebral Blood Vessels: Comparison with Aminergic and Cholinergic Nerve Fibers

1984 ◽  
Vol 4 (3) ◽  
pp. 407-414 ◽  
Author(s):  
Toru Itakura ◽  
Takashi Okuno ◽  
Kazuo Nakakita ◽  
Ichiro Kamei ◽  
Yutaka Naka ◽  
...  
Keyword(s):  
Substance P ◽  
Blood Vessels ◽  
Vasoactive Intestinal Polypeptide ◽  
Electron Microscopic Observation ◽  
Nerve Fibers ◽  
Muscle Control ◽  
Cerebral Blood Vessels ◽  
Electron Microscopic ◽  
Cholinergic Nerve Fibers ◽  
Intestinal Polypeptide

Vasoactive intestinal polypeptide (VIP)– and substance P–containing nerve fibers were observed in the cerebral blood vessels using an immunohistochemical technique. VIP-containing nerve fibers distributed in a spiral pattern, similar to that of muscle cells. Under electron microscopic observation, VIP-immunoreactive terminals lay close to a muscle cell in the inner layer of the adventitia. In contrast, substance P–containing nerve fibers showed a meshwork pattern in the outer layer of the adventitia. Using both acetylcholinesterase (AChE) staining and VIP immunohistochemistry, AChE-positive and VIP-immunoreactive nerve fibers revealed almost the same distribution in the same specimen. The present data suggest that VIP-containing nerve fibers may play a role in the smooth muscle control of the blood vessels, whereas substance P–containing nerve fibers may not take part in muscle control.

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