Somatostatin inhibition of secretagogue and forskolin-stimulated gastric acid secretion

1988 ◽  
Vol 254 (4) ◽  
pp. G531-G537
Author(s):  
F. Michelangeli ◽  
M. C. Ruiz ◽  
C. L. Rodriguez ◽  
A. Pelacca
Keyword(s):  
Acid Secretion ◽  
Histamine Release ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Direct Stimulation ◽  
Histamine Stimulation ◽  
Ussing Chambers ◽  
Cyclic Monophosphate ◽  
Dose Dependent ◽  
Stimulation Of

The action of somatostatin (SS) on acid secretion and histamine release was studied in isolated gastric mucosa of toads mounted in Ussing chambers. SS inhibited H+ secretion and histamine release stimulated by cholinergic and gastrinergic secretagogues. Exogenous histamine stimulation of H+ secretion was blocked noncompetitively by SS in a dose-dependent manner. In mucosae maximally stimulated by histamine or forskolin and cimetidine, acetylcholine (ACh) and tetragastrin (TG) induced a direct stimulation of the oxyntopeptic cell not inhibited by SS. Indomethacin, an inhibitor of prostaglandin synthesis, did not prevent SS inhibition of histamine stimulation. Pretreatment with SS abolished forskolin stimulation of H+ secretion. SS induced a small inhibition of the stimulatory effect of N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. These results suggest that SS inhibits acid secretion stimulated by secretagogues through different mechanisms: 1) inhibition of histamine release by ACh and TG, 2) inhibition of endogenous and exogenous histamine stimulation through a blockade of adenylate cyclase, and 3) an inhibitory effect subsequent to the synthesis of adenosine 3',5'-cyclic monophosphate. The direct activation of the oxyntopeptic cell by ACh and TG does not seem to be affected by somatostatin.

Regulation of PI hydrolysis and cAMP formation by muscarinic M3 receptor in guinea pig gallbladder

1994 ◽  
Vol 267 (4) ◽  
pp. G523-G528
Author(s):  
T. Takahashi ◽  
S. Kurosawa ◽  
C. Owyang
Keyword(s):  
Guinea Pig ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Biochemical Responses ◽  
Muscarinic Receptor Antagonists ◽  
M3 Receptor ◽  
Pi Hydrolysis ◽  
Dose Dependent ◽  
Camp Formation ◽  
Stimulation Of

Carbachol (10(-8)-10(-3) M) produced two distinct biochemical responses in the guinea pig gallbladder smooth muscle: simulation of phosphoinositide (PI) hydrolysis and inhibition of forskolin-mediated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The mean effective dose (ED50) concentration (1.6 x 10(-5) M) of carbachol-mediated stimulation of PI hydrolysis was 145 times greater than the ED50 concentration (1.1 x 10(-7) M) of carbachol mediated inhibition of cAMP formation. The inhibitory effect of carbachol on cAMP formation was antagonized by the pretreatment of pertussis toxin. To determine whether these two biochemical responses were mediated by the same or different subtypes of muscarinic receptors, the relative potencies of muscarinic receptor antagonists were calculated by Schild analysis. The M3 muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) exhibited inhibitory constant (Ki) values at 0.3 and 1.2 nM in antagonizing the stimulation of PI hydrolysis and the inhibition of cAMP formation, respectively. The corresponding Ki values for pirenzepine, a muscarinic M1 antagonist, were 11 and 130 nM. The corresponding Ki values for AF-DX 116, a muscarinic M2 antagonist, were 34 and 450 nM. Thus 4-DAMP was 37x and 108x more potent than pirenzepine in antagonizing the stimulation of PI hydrolysis and the inhibition of cAMP formation, respectively. In addition, compared with AF-DX 116, 4-DAMP was 113x and 375x more potent in reducing stimulation of PI hydrolysis and inhibition of cAMP formation. Cholecystokinin (CCK) octapeptide (10(-10)-(10-6) M) caused a significant increase of PI hydrolysis but had no inhibitory effects on cAMP formation evoked by forskolin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach

1981 ◽  
Vol 240 (3) ◽  
pp. E274-E278
Author(s):  
Y. Goto ◽  
M. Berelowitz ◽  
L. A. Frohman
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Rat Stomach ◽  
Beta Adrenergic ◽  
Somatostatin Secretion ◽  
Adrenergic Mechanism ◽  
Dose Dependent

The secretion of somatostatin-like immunoreactivity (SRIF-LI) by the isolated perfused rat stomach was studied in response to stimulation by catecholamines. Gastric SRIF-LI secretion was significantly stimulated in a dose-dependent manner by norepinephrine at 10(-6) and 10(-8) M, and the effect of norepinephrine (10(-8) M) was attenuated by the addition of propranolol (10(-6) M) but not of phentolamine (10(-6) M). SRIF-LI secretion was also stimulated by dopamine at concentrations of 10(-4) and 10(-6) M but not at 10(-8) M. The effect of dopamine (10(-6) M) was not altered by the addition of haloperidol (10(-4) to 10(-7)) or metoclopramide (10(-4) M), and bromocriptine (10(-6) M) was without effect on SRIF-LI secretion. These results suggest that gastric SRIF-LI secretion is stimulated by a beta-adrenergic mechanism and raise the possibility that gastric somatostatin contributes to the inhibitory effect of norepinephrine on gastric acid secretion.

Effect of somatolactin and related hormones on phosphate transport by flounder renal tubule primary cultures

1995 ◽  
Vol 268 (3) ◽  
pp. R577-R582 ◽  
Author(s):  
M. Lu ◽  
P. Swanson ◽  
J. L. Renfro
Keyword(s):  
Primary Cultures ◽  
Phosphate Transport ◽  
Specific Protein ◽  
Dependent Manner ◽  
Initial Exposure ◽  
Ussing Chambers ◽  
Cyclic Monophosphate ◽  
Primary Monolayer ◽  
Dose Dependent ◽  
Primary Monolayer Cultures

Winter flounder renal proximal tubule primary monolayer cultures mounted in Ussing chambers were used to determine the effect of salmon somatolactin (sSL) on transepithelial Pi and Ca2+ transport. sSL stimulated Pi reabsorption in a dose-dependent manner at physiological levels of the hormone (12.5 ng/ml). Net Pi transport was significantly altered by sSL (200 ng/ml) within 2 h after the initial exposure. Ca2+ fluxes were unchanged by the addition of 200 ng/ml sSL. The sSL-induced Pi reabsorption was abolished by 10 microM H-89, a highly specific protein kinase A inhibitor. Moreover the production and release of adenosine 3',5'-cyclic monophosphate were significantly increased after 1 and 2 h of exposure to sSL. The data indicate that sSL directly stimulates net renal Pi reabsorption by an adenosine 3',5'-cyclic monophosphate-dependent pathway. In addition to sSL, flounder SL and rat prolactin greatly, and salmon growth hormone (2.3 micrograms/ml) slightly, increased net Pi reabsorptive flux, whereas salmon prolactin had no effect.

scholarly journals Reflex cardiovascular responses originating in exercising muscles of mice

2001 ◽  
Vol 90 (2) ◽  
pp. 579-585 ◽  
Author(s):  
Jeffery M. Kramer ◽  
Arthur Aragones ◽  
Tony G. Waldrop
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Muscle Contraction ◽  
Cardiovascular Responses ◽  
Muscular Contraction ◽  
Dependent Manner ◽  
Direct Stimulation ◽  
Systemic Hypoxia ◽  
Dose Dependent ◽  
Stimulation Of

The cardiovascular responses induced by exercise are initiated by two primary mechanisms: central command and reflexes originating in exercising muscles. Although our understanding of cardiovascular responses to exercise in mice is progressing, a murine model of cardiovascular responses to muscle contraction has not been developed. Therefore, the purpose of this study was to characterize the cardiovascular responses to muscular contraction in anesthetized mice. The results of this study indicate that mice demonstrate significant increases in blood pressure (13.8 ± 1.9 mmHg) and heart rate (33.5 ± 11.9 beats/min) to muscle contraction in a contraction-intensity-dependent manner. Mice also demonstrate 23.1 ± 3.5, 20.9 ± 4.0, 21.7 ± 2.6, and 25.8 ± 3.0 mmHg increases in blood pressure to direct stimulation of tibial, peroneal, sural, and sciatic hindlimb somatic nerves, respectively. Systemic hypoxia (10% O2-90% N2) elicits increases in blood pressure (11.7 ± 2.6 mmHg) and heart rate (42.7 ± 13.9 beats/min), while increasing arterial pressure with phenylephrine decreases heart rate in a dose-dependent manner. The results from this study demonstrate the feasibility of using mice to study neural regulation of cardiovascular function during a variety of autonomic stimuli, including exercise-related drives such as muscle contraction.

Pharmacological characterization of histamine H3 receptors in isolated rabbit gastric glands

1992 ◽  
Vol 262 (1) ◽  
pp. G56-G61 ◽  
Author(s):  
A. Bado ◽  
L. Moizo ◽  
J. P. Laigneau ◽  
M. J. Lewin
Keyword(s):  
Acid Secretion ◽  
Histamine Release ◽  
Secretory Process ◽  
Dependent Manner ◽  
Gastric Glands ◽  
Pharmacological Characterization ◽  
H2 Antagonist ◽  
H3 Receptors ◽  
Dose Dependent

The effects of the specific H3 agonist (R)-alpha-methylhistamine (alpha-MeHA) and the specific H3 antagonist thioperamide were examined on histamine release and acid secretion [( 14C]-aminopyrine (AP) accumulation) by isolated rabbit gastric glands. Thioperamide significantly enhanced basal histamine release from the glands (+50% at 30 min for 10(-7) M thioperamide; P less than 0.01), and this increase was prevented by alpha-MeHA. Histamine-elicited AP accumulation was increased by 18% (P less than 0.05) by 10(-7) M thioperamide and decreased by 70% (P less than 0.01) by 10(-6) M of the H2 antagonist ranitidine. Thioperamide alone significantly enhanced AP accumulation in a dose-dependent manner, whereas alpha-MeHA had no effect of its own on this accumulation. Thioperamide stimulation of basal AP accumulation was not modified by ranitidine but was 50% decreased by alpha-MeHA. Furthermore, carbachol-induced AP accumulation was decreased by alpha-MeHA and increased by thioperamide; the latter effect was not blocked by ranitidine. These findings support that H3 receptors pharmacologically distinct from H2 receptors are involved in the regulation of histamine-stimulated acid secretion. They further suggest that these gastric H3 receptors occur in the gastric glands as 1) H3 autoreceptors located on the histamine-secreting cells and acting to downregulate histamine release from these cells and 2) H3 (or H3-like) receptors located on the parietal cell and regulating in a negative manner the acid secretory process.

Synthesis and Assessment of Novel Anti-chlamydial Benzylidene Acylhydrazides Derivatives

2018 ◽  
Vol 15 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Xiaofeng Bao ◽  
Ying Xue ◽  
Chao Xia ◽  
Yin Lu ◽  
Ningjing Yang ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dependent Manner ◽  
Iron Starvation ◽  
Hydrochloride Salt ◽  
Obligate Intracellular ◽  
Biphasic Life Cycle ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Dose Dependent ◽  
Better Than

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

Reversible arrest of Artemia development by cadmium

1986 ◽  
Vol 64 (8) ◽  
pp. 1633-1641 ◽  
Author(s):  
Parvaneh Rafiee ◽  
Christopher O. Matthews ◽  
Joseph C. Bagshaw ◽  
Thomas H. MacRae
Keyword(s):  
Normal Development ◽  
Developmental Process ◽  
Inhibitory Effect ◽  
Microtubule Assembly ◽  
Abnormal Development ◽  
Dependent Manner ◽  
Physiological Changes ◽  
Molecular Aspects ◽  
Reduced Rate ◽  
Dose Dependent

Under normal conditions, an encysted Artemia embryo undergoes a developmental process that culminates in the gradual, uninterrupted emergence of the prenauplius from the cyst. The hatching membrane surrounding the emerged organism is then ruptured, usually beginning at the posterior end, and a motile nauplius is released. We have observed this process microscopically in the presence and absence of cadmium and report that cadmium disrupts Artemia development in a dose–dependent manner. At 0.1 μM, cadmium slows emergence but nauplii eventually resume rellatively normal development. Emergence and hatching are either delayed considerably or almost entirely prevented at 1 μM cadmium. Cadmium at 10 μM, completely arrests emergence but development continues at a reduced rate, eventually resulting in hatching of some organisms without need for complete emergence. If organisms exposed to 10 μM cadmium are washed, abnormally shaped emerged forms are released and many of these eventually hatch, although in an unusual manner. Cadmium at 10 μM causes complete, rapid precipitation of purified Artemia tubulin at 0 °C but cadmium at the lower concentrations tested has no apparent inhibitory effect on microtubule assembly. Although we do not know the actual cadmium–induced physiological changes that result in abnormal development of Artemia, our results indicate that we can now examine the interdependence of morphological and molecular aspects of Artemia development in a way not previously possible.

Prostaglandin E2-histamine in interactions on cAMP, cGMP, and acid production in isolated fundic glands

1982 ◽  
Vol 242 (1) ◽  
pp. G21-G26 ◽  
Author(s):  
R. A. Levine ◽  
K. R. Kohen ◽  
E. H. Schwartzel ◽  
C. E. Ramsay
Keyword(s):  
Prostaglandin E2 ◽  
Acid Secretion ◽  
Acid Production ◽  
Camp Production ◽  
Histamine Stimulation ◽  
Fundic Mucosa ◽  
Biochemical Responses ◽  
Camp Levels ◽  
Camp And Cgmp ◽  
Stimulation Of

Relations among cAMP, cGMP, acid production [measured by the intraglandular accumulation of [14C]aminopyrine (AP)], and prostaglandin E2 (PGE2) activity were studied in isolated glands from rabbit fundic mucosa. AP, cAMP, and cGMP responses to histamine, PGE2, and 3-isobutyl-1-methylxanthine (IMX) were compared with controls. Histamine and PGE2 significantly increased glandular cAMP levels twofold, and histamine and IMX stimulated AP uptake two- to fourfold. PGE2 significantly inhibited both histamine- and IMX-stimulated AP accumulation, but it did not alter basal AP uptake. PGE2 also decreased histamine-stimulated cAMP production but only at a low concentration (10(-7) M). This dose of PGE2 was near to the endogenous PGE2 content found in unstimulated glands (10(-8) M). Intraglandular cGMP levels in unstimulated glands (10(-8) M). Intraglandular cGMP levels were increased by IMX but not by PGE2 or histamine. It is concluded that histamine stimulation of acid secretion is mediated by cAMP, that secretory and biochemical responses to histamine are modulated by PGE2 because PGE2 antagonized histamine-stimulated cAMP and AP uptake, and that the rise in cAMP induced solely by PGE2 appears to be localized within nonparietal cells because PGE2 alone did not stimulate AP accumulation.

Sign in / Sign up

Export Citation Format

Share Document