Potent stimulation of glycoprotein secretion in canine trachea by substance P

1984 ◽  
Vol 57 (5) ◽  
pp. 1323-1327 ◽  
Author(s):  
S. J. Coles ◽  
K. H. Neill ◽  
L. M. Reid
Keyword(s):  
Substance P ◽  
Time Course ◽  
Collecting Duct ◽  
Regulatory Peptides ◽  
Submucosal Gland ◽  
Airway Mucosa ◽  
Glycoprotein Secretion ◽  
Median Effective Concentration ◽  
Stimulation Of

The effects have been investigated of the regulatory peptides, substance P (SP) and bombesin, on the secretion of [14C]glucosamine-labeled trichloroacetic acid-phosphotungstic acid precipitable glycoproteins by canine tracheal explants. SP (10(10) to 10(-7) M) induced a dose-dependent increase in secretion of high-molecular-weight (greater than 2 X 10(6) radiolabeled glycoproteins predominantly from the submucosal glands. On a molar basis, SP [median effective concentration (EC50) = 8.2 X 10(-10) M] was about 1,000-fold more potent than methacholine (EC50 = 6.3 X 10(-7) M). Bombesin (10(-10) to 10(-4) M) had no effect on glycoprotein secretion. The time course of SP effect was characterized by an initial stimulation of glycoprotein secretion followed by a period of inhibition, suggesting that it rapidly exhausts a pool of glycoprotein, possibly that present within the duct lumen of the submucosal gland. Consistent with this are the findings that SP-induced secretion of glycoprotein was augmented by preincubation with methacholine while methacholine-induced secretion was diminished by preincubation with SP. Our findings show that SP is a potent stimulant of airway glycoprotein secretion in vitro and suggest that it acts by increasing the rate of clearance of mucus from the ducts of the submucosal gland, possibly by induced constriction of the secretory tubules and collecting duct. A role is discussed for SP in mucus hypersecretion induced by local axonal reflexes in the airway mucosa.

Effect of neuropeptides released from sensory nerves on blood flow in the rat airway microcirculation

1992 ◽  
Vol 72 (4) ◽  
pp. 1563-1570 ◽  
Author(s):  
G. Piedimonte ◽  
J. I. Hoffman ◽  
W. K. Husseini ◽  
W. L. Hiser ◽  
J. A. Nadel
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Regional Blood Flow ◽  
Reference Sample ◽  
Left Ventricular ◽  
Sensory Nerves ◽  
Microvascular Blood Flow ◽  
Systemic Injection ◽  
Airway Mucosa ◽  
Stimulation Of

Stimulation of sensory nerves in the airway mucosa causes local release of the neuropeptides substance P and calcitonin gene-related peptide (CGRP). In this study we used a modification of the reference-sample microsphere technique to measure changes in regional blood flow and cardiac output distribution produced in the rat by substance P, CGRP, and capsaicin (a drug that releases endogenous neuropeptides from sensory nerves). Three sets of microspheres labeled with different radionuclides were injected into the left ventricle of anesthetized F344 rats before, immediately after, and 5 min after left ventricular injections of capsaicin, substance P, or CGRP. The reference blood sample was withdrawn from the abdominal aorta and was simultaneously replaced with 0.9% NaCl at 37 degrees C. We found that stimulation of sensory nerves with a low dose of capsaicin causes a large and selective increase in microvascular blood flow in the extrapulmonary airways. The effect of capsaicin is mimicked by systemic injection of substance P but not by CGRP, suggesting that substance P is the main agent of neurogenic vasodilation in rat airways.

scholarly journals Stimulus-secretion coupling in the neurohypophysis of the jerboa Jaculus orientalis.

1994 ◽  
Vol 195 (1) ◽  
pp. 19-34
Author(s):  
A Raji ◽  
J J Nordmann
Keyword(s):  
Time Course ◽  
Physiological State ◽  
Nerve Endings ◽  
Neurosecretory System ◽  
Channel Blockers ◽  
Vasopressin Release ◽  
Oxytocin Release ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

1. In many mammals, severe dehydration is known to cause exhaustion of the vasopressin content of the neural lobe. Here, we have examined the physiological state of the neurohypophysis of the jerboa Jaculus orientalis, a rodent inhabitant of a semi-desert climate. 2. Isolated neurohypophyses and neurosecretory nerve endings were perfused in vitro and vasopressin and oxytocin release were determined by radioimmunoassay. 3. Electrical stimulation of the neurohypophysis with bursts of pulses mimicking the activity of hypersecreting neuroendocrine neurones induced similar increases of secretion in both control animals and animals dehydrated for up to 2 months. Neurohormone release was greatly potentiated when the bursts of pulses were separated by silent intervals. 4. Prolonged stimulation of neurohypophyses from both control and dehydrated animals induced a sustained increase of vasopressin release; in contrast, oxytocin release under similar conditions showed a biphasic secretory pattern consisting of a transient increase that subsequently decreased to a steady level whose amplitude was similar to that for vasopressin. 5. K(+)-induced secretion was largely inhibited by the Ca2+ channel blockers nicardipine and omega-conotoxin, suggesting that in this neurosecretory system both L- and N-type calcium channels play a major role in stimulus-secretion coupling. Depolarization of isolated nerve endings using a fast-flow perifusion system showed that there was no difference in the amplitude and the time course of the secretory response in dehydrated and hydrated animals. 6. The results demonstrate that, despite the climatic conditions in which the jerboas live, their neural lobes retain the capacity to release, upon depolarization of the plasma membrane of the nerve endings, large amounts of neurohormone. It is concluded that the neurohypophyseal peptidergic release system in the dehydrated jerboa functions adequately even under extreme environmental stress.

Excretion in the house cricket: stimulation of rectal reabsorption by homogenates of the corpus cardiacum

1993 ◽  
Vol 185 (1) ◽  
pp. 305-323 ◽  
Author(s):  
J. H. Spring ◽  
S. A. Albarwani
Keyword(s):  
Time Course ◽  
Chloride Transport ◽  
Malpighian Tubule ◽  
Acheta Domesticus ◽  
Rectal Absorption ◽  
K Uptake ◽  
House Cricket ◽  
Tubule Fluid ◽  
Stimulation Of

1. We describe an in vitro perfused preparation of Acheta domesticus rectum which allows direct comparison of Malpighian tubule secretion and rectal absorption under identical conditions. Rectal absorption is stimulated four- to sixfold by corpora cardiaca (CC) homogenates and the stimulated rate is sufficiently rapid to account for all the fluid secreted by the tubules. 2. The time course for increased fluid absorption is similar to that required to stimulate electrogenic chloride transport in locusts and grasshoppers. Chloride is rapidly absorbed by the rectum under all conditions, along with lesser amounts of Na+ and K+. Unlike the situation in locusts, K+ uptake is unaffected by CC homogenates and the stimulated absorbate is NaCl-rich, similar in composition to the NaCl-rich tubule fluid produced under stimulated conditions. The absorbate is always slightly hypo-osmotic to the perfusate, reaching a maximum differential of approximately 15 mosmol l-1 following CC stimulation. 3. The antidiuretic factor that reduces tubule secretion does not promote fluid reabsorption by the rectum.

Stimulation of total CO2 flux by 10% CO2 in rabbit CCD: role of an apical Sch-28080- and Ba-sensitive mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. F114-F120 ◽  
Author(s):  
X. Zhou ◽  
C. S. Wingo
Keyword(s):  
Collecting Duct ◽  
Co2 Flux ◽  
K Channel ◽  
Co2 Absorption ◽  
Cortical Collecting Duct ◽  
Atpase Inhibitor ◽  
Contrast Exposure ◽  
Stimulation Of

These studies examine the effect of ambient PCO2 on net bicarbonate (total CO2) absorption by the in vitro perfused cortical collecting duct (CCD) from K-replete rabbits and the mechanism responsible for this effect. Exposure to 10% CO2 increased net bicarbonate flux (total CO2 flux, JtCO2) by 1.8-fold (P < 0.005), and this effect was inhibited by luminal 10 microM Sch-28080, an H-K-adenosinetriphosphatase (H-K-ATPase) inhibitor. In contrast, exposure to 10% CO2 significantly decreased Rb efflux, and this decrement in Rb efflux was blocked by luminal 2 mM Ba, a K channel blocker. Thus transepithelial tracer Rb flux did not increase upon exposure to 10% CO2 as we have observed in this segment under K-restricted conditions. The observation that 10% CO2 increased net bicarbonate absorption without a change in absorptive Rb flux suggested that 10% CO2 increased apical K recycling. To test this hypothesis, we examined whether luminal Ba inhibited the stimulation of luminal acidification induced by 10% CO2. If apical K exit were necessary for full activation of proton secretion, then inhibiting K exit should indirectly affect the stimulation of JtCO2 by 10% CO2. In fact, the effect of 10% CO2 on JtCO2 in the presence of 2 mM luminal Ba was quantitatively indistinguishable from the effect of 10% CO2 on JtCO2 in the presence of 10 microM luminal Sch-28080.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Overexpression of membrane metalloendopeptidase inhibits substance P stimulation of cholangiocarcinoma growth

2014 ◽  
Vol 306 (9) ◽  
pp. G759-G768 ◽  
Author(s):  
Fanyin Meng ◽  
Sharon DeMorrow ◽  
Julie Venter ◽  
Gabriel Frampton ◽  
Yuyan Han ◽  
...  
Keyword(s):  
Substance P ◽  
Functional Role ◽  
Xenograft Model ◽  
Subsequent Increase ◽  
Proliferation In Vitro ◽  
Proteolytic Product ◽  
Stimulation Of

Substance P (SP) promotes cholangiocyte growth during cholestasis by activating its receptor, NK1R. SP is a proteolytic product of tachykinin (Tac1) and is deactivated by membrane metalloendopeptidase (MME). This study aimed to evaluate the functional role of SP in the regulation of cholangiocarcinoma (CCA) growth. NK1R, Tac1, and MME expression and SP secretion were assessed in human CCA cells and nonmalignant cholangiocytes. The proliferative effects of SP (in the absence/presence of the NK1R inhibitor, L-733,060) and of L-733,060 were evaluated. In vivo, the effect of L-733,060 treatment or MME overexpression on tumor growth was evaluated by using a xenograft model of CCA in nu/nu nude mice. The expression of Tac1, MME, NK1R, PCNA, CK-19, and VEGF-A was analyzed in the resulting tumors. Human CCA cell lines had increased expression of Tac1 and NK1R, along with reduced levels of MME compared with nonmalignant cholangiocytes, resulting in a subsequent increase in SP secretion. SP treatment increased CCA cell proliferation in vitro, which was blocked by L-733,060. Treatment with L-733,060 alone inhibited CCA proliferation in vitro and in vivo. Xenograft tumors derived from MME-overexpressed human Mz-ChA-1 CCA cells had a slower growth rate than those derived from control cells. Expression of PCNA, CK-19, and VEGF-A decreased, whereas MME expression increased in the xenograft tumors treated with L-733,060 or MME-overexpressed xenograft tumors compared with controls. The study suggests that SP secreted by CCA promotes CCA growth via autocrine pathway. Blockade of SP secretion and NK1R signaling may be important for the management of CCA.

Substance P contracts bovine tracheal smooth muscle via activation of myosin light chain kinase

1990 ◽  
Vol 259 (2) ◽  
pp. C258-C265 ◽  
Author(s):  
M. A. Corson ◽  
J. R. Sellers ◽  
R. S. Adelstein ◽  
M. Schoenberg
Keyword(s):  
Substance P ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Time Course ◽  
Myosin Light Chain ◽  
Immunoblot Analysis ◽  
Isometric Tension ◽  
Peak Tension ◽  
Tension Response

At near-threshold substance P concentrations, the isometric tension response of bovine tracheal strips is almost completely abolished by atropine, indicating mediation of contraction via substance P-stimulated release of acetylcholine from prejunctional nerve terminals. At near-maximal concentrations, the atropine-inhibited component of the tension response is less than 25%, indicating mainly direct activation. Under conditions in which activation by substance P is direct, peak tension is reached in approximately 11 min. Immunoblot analysis of the time course of phosphorylation of the 20-kDa myosin light chain (LC20) reveals incorporation of approximately 0.5 mol phosphate/mol light chain at 10 min. Two-dimensional tryptic phosphopeptide analysis of phosphorylated light chain reveals a single major phosphopeptide. The peptide migrates identically with that produced by myosin light chain kinase phosphorylation of purified tracheal myosin in vitro. Contraction stimulated by acetylcholine is more rapid, with attainment of peak tension in 2.5 min and a peak LC20 phosphorylation of 0.65 mol/mol. These results indicate that 1) substance P mediates contraction of bovine trachea both directly and indirectly, and 2) under conditions in which activation is direct, the tension and phosphorylation responses qualitatively resemble those observed with acetylcholine.

Cellular mechanisms mediating the stimulation of ovine endometrial secretion of prostaglandin F2α in response to oxytocin: role of phospholipase C and diacylglycerol

1994 ◽  
Vol 141 (3) ◽  
pp. 481-490 ◽  
Author(s):  
W J Silvia ◽  
J-S Lee ◽  
D S Trammell ◽  
S H Hayes ◽  
L L Lowberger ◽  
...  
Keyword(s):  
Time Course ◽  
Prostaglandin F2α ◽  
Endometrial Tissue ◽  
Indole Derivatives ◽  
Cellular Mechanisms ◽  
Response Curves ◽  
The Relationship ◽  
Stimulation Of

Abstract The first objective was to describe and evaluate the relationship between the ability of oxytocin to stimulate the activity of phospholipase (PL) C and its ability to stimulate the release of prostaglandin (PG) F2α in ovine endometrial tissue. Caruncular endometrial tissue was collected from ovariectomized ewes after completion of an 11-day steroid replacement protocol. In experiment 1, explants were incubated either in the presence (10−6 m) or absence of oxytocin for 0, 1, 3, 10, 30 or 100 min to examine the time-course for activation of PLC and release of PGF2α in response to oxytocin. An increase in the activity of PLC was detected at 3 min while an increase in the release of PGF2α was not detected until 10 min (P<0·05). In experiment 2, explants were incubated in the presence of various oxytocin analogues (10−6 m) to compare their abilities to activate PLC and release PGF2α. Oxytocin and three receptor angonists stimulated the activity of PLC and the release of PGF2α (P<0·05) while two oxytocin receptor antagonists had no effect on either response. In experiment 3, explants were incubated in the presence of oxytocin or arginine vasopressin at 10−9 to 10−6 m to establish dose–response curves for the activation of PLC and release of PGF2α. For both hormones, significant increases (P<0·05) in the release of PGF2α were observed at 10−8 m while increases in PLC activity were not detected until 10−7 m was used. In experiment 4, explants were pretreated with either U-73122 (an inhibitor of PLC activity) or U-73343 (an inactive analogue of U-73122). Explants were then treated with control medium, oxytocin or AlF4−. Both oxytocin and AlF4− stimulated the activity of PLC and the release of PGF2α (P<0·05). U-73122 blocked the ability of oxytocin to stimulate the release of PGF2α (P<0·05) but had no effect on its ability to stimulate the activity of PLC (P>0·1). Based on the results from these experiments, the role of PLC in mediating the stimulatory effect of oxytocin on the release of PGF2α remains unclear. The second objective was to evaluate the role of diacylglycerol (DAG) in mediating the stimulatory effect of oxytocin on endometrial secretion of PGF2α. In experiment 5, explants were incubated in vitro with varying doses of two DAG analogues. Both analogues stimulated the release of PGF2α at 10−6 m (P<0·05), the highest dose tested. Corresponding inactive control compounds had no stimulatory effect. In experiment 6, explants were incubated with two synthetic DAGs and two indole-derived analogues of DAG. The indole derivatives stimulated the release of PGF2α. The synthetic DAGs were less effective in stimulating the release of PGF2α at the doses tested. In experiment 7, explants were preincubated with R59022 or LiCl. R59022 enhanced both the basal and oxytocin-stimulated released of PGF2α (P=0·07). LiCl promoted an increase in the accumulation of inositol trisphosphate (P<0·05) but had no effect on the release of PGF2α (P>0·5). These data indicate that DAG stimulates release of PGF2α from ovine endometrial tissue and may mediate the stimulatory effect of oxytocin on release of PGF2α. Journal of Endocrinology (1994) 141, 481–490

scholarly journals Vasopressin-induced differential stimulation of AQP4 splice variants regulates the in-membrane assembly of orthogonal arrays

2009 ◽  
Vol 296 (6) ◽  
pp. F1396-F1404 ◽  
Author(s):  
Alfred N. Van Hoek ◽  
Richard Bouley ◽  
YingXian Lu ◽  
Claudia Silberstein ◽  
Dennis Brown ◽  
...  
Keyword(s):  
Splice Variant ◽  
Splice Variants ◽  
Collecting Duct ◽  
Dominant Role ◽  
Water Channel ◽  
Membrane Expression ◽  
Expression Levels ◽  
Stimulation Of

Aquaporin-4 (AQP4) is a basolateral water channel in collecting duct principal cells and assembles into orthogonal array particles (OAPs), the size of which appears to depend on relative expression levels of AQP4 splice variants. Because the higher-order organization of AQP4 was perturbed by vasopressin in Brattleboro rats and phosphorylation sites have been identified on AQP4, we investigated whether vasopressin and forskolin (Fk) affect AQP4 assembly and/or expression in LLC-PK1 cells stably transfected with the AQP4 splice variant M23, which is responsible for formation of OAPs, and/or the splice variant M1, which does not form OAPs. Our data show that [lys8]-vasopressin (LVP) and Fk treatment led to differential increases in expression levels of M23-AQP4 and M1-AQP4 that varied as a function of incubation time. At early time points ( day 1) expression of M1 was significantly stimulated (4.5-fold), over that of M23 (1.6-fold), but after 3 days the expression of M23 became predominant (4.1-fold) over that of M1 (1.9-fold). This pattern of stimulation was dependent on an intact AQP4 residue serine 111 and required protein synthesis. In cells expressing both M1 and M23 (M1/M23 ∼ 1), with small sized OAPs at the membrane, the LVP/Fk-induced stimulation of M23 was modified and mimicked that of M1 when expressed alone, suggesting a dominant role for M1. In Brattleboro kidney inner medulla, an 8-day chronic exposure to the vasopressin agonist (dDAVP) led to reduction in M1 and a significant increase in M23 immunoblot staining (M1/M23 = 2/3 → 1/4). These results indicate that AQP4 organization and expression are regulated by vasopressin in vivo and in vitro and demonstrate that the dominant role for M1 is restricted to a one-to-one interaction between AQP4 splice variants that regulates the membrane expression of OAPs.

Epithelial vs. serosal stimulation of tracheal muscle: role of epithelium

1989 ◽  
Vol 67 (6) ◽  
pp. 2522-2526 ◽  
Author(s):  
D. Pavlovic ◽  
M. Fournier ◽  
M. Aubier ◽  
R. Pariente
Keyword(s):  
Time Course ◽  
Muscle Tension ◽  
Active Role ◽  
Force Transducer ◽  
Tension Development ◽  
In Vitro System ◽  
Pharmacological Stimulation ◽  
Stimulation Of

There is evidence implying an active role of airway epithelium in the modulation of bronchomotor tone. To study this phenomenon, we designed an in vitro system allowing pharmacological stimulation of either the inside or outside of the airway lumen. Rat tracheas were excised, cannulated, and their inside and outside perfused independently with Krebs solution. Two hooks were inserted through opposite sides of the tracheal wall, the lower one was attached to a fixed point, while the upper one was connected to a force transducer. Isometric contractions of the tracheal muscle were elicited by carbachol solution perfused in single and cumulative concentrations. In one-half of the preparations the epithelium was mechanically removed. Stimulation of the inside or outside of the trachea produced equal maximal tracheal muscle tension [1.55 +/- 0.14 and 1.2 +/- 0.09 (SE) g in and out, respectively]. The time course of tension development was longer when carbachol was administered inside the trachea: an effect that was abolished when the epithelium was removed. In addition, removal of the epithelium was found 1) to increase the maximal tension irrespective of the route of carbachol perfusion and 2) to increase the sensitivity of the preparation to carbachol stimulation.

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