scholarly journals Vasoactive intestinal peptide (VIP) stimulates cortisol secretion from the H295 human adrenocortical tumour cell line via VPAC1 receptors

2004 ◽  
Vol 32 (3) ◽  
pp. 869-877 ◽  
Author(s):  
MR Nicol ◽  
VJ Cobb ◽  
BC Williams ◽  
SD Morley ◽  
SW Walker ◽  
...  
Keyword(s):  
Cell Line ◽  
Vasoactive Intestinal Peptide ◽  
Receptor Agonist ◽  
Threshold Dose ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cortisol Secretion ◽  
Maximal Dose ◽  
Vpac1 Receptor ◽  
Dose Dependent

Vasoactive intestinal peptide (VIP) shows a wide tissue distribution and exerts numerous physiological actions. VIP was shown in a dose-dependent manner to increase cortisol secretion in the NCI-H295R human adrenocortical carcinoma (H295) cell line (threshold dose 3.3x10(-10) M, maximal dose 10(-7) M), coupled with a parallel increase in cAMP accumulation. Receptor-specific agonists were employed to determine which of the two known VIP receptor subtypes was involved in cortisol secretion. Treatment with the VPAC1 receptor agonist, [K(15), R(16), L(27)]VIP(1-7)/GRF(8-27), produced a dose-dependent increase in H295 cell cortisol secretion (threshold dose 10(-11) M, maximal dose 10(-7) M) similar to that seen with VIP. Meanwhile, the high-affinity VPAC2 receptor agonist, RO-25-1553, failed to stimulate significantly cortisol or cAMP production from H295 cells. Inhibition of VIP-mediated H295 cell cortisol secretion by PG97-269, a competitive VPAC1-specific antagonist, produced parallel shifts of the dose-response curve and a Schild regression slope of 0.99, indicating competitive inhibition at a single receptor subtype. VIP is known also to interact with the PAC1 receptor, albeit with lower affinity (EC(50) of approximately 200 nM) than the homologous ligand, PACAP (EC(50) of approximately 0.5 nM). PACAP stimulated cortisol secretion from H295 cells (EC(50) of 0.3 nM), suggesting the presence of functional PAC1 receptors. However, stimulation of cortisol secretion by nanomolar concentrations of VIP (EC(50) of 5 nM), coupled with real-time PCR estimation that VPAC1 receptor transcripts appear 1000-fold more abundant than PAC1 transcripts in H295 cells, makes it unlikely that VIP signals via PAC1 receptors. Together, these data suggest that VIP directly stimulates cortisol secretion from H295 cells via activation of the VPAC1 receptor subtype.

Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane

1994 ◽  
Vol 72 (2) ◽  
pp. 168-173 ◽  
Author(s):  
Daniel Abran ◽  
Daya R. Varma ◽  
Ding-You Li ◽  
Sylvain Chemtob
Keyword(s):  
Blood Flow ◽  
Receptor Agonist ◽  
Perfusion Pressure ◽  
Retinal Blood Flow ◽  
Receptor Subtype ◽  
Retinal Vasculature ◽  
Receptor Subtypes ◽  
Retinal Vessels ◽  
Limit Blood Flow ◽  
Arteries And Veins

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2α, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2α and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2α and PGE2, the thromboxane analogue, U46619, as well as the α1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult. Our findings indicate that the retinal vasculature of the newborn responds minimally to prostaglandins, primarily PGF2α and PGE2, compared with the adult, but constricts effectively to thromboxane. Since prostaglandins play an important role in the autoregulation of retinal blood flow, our observations provide an explanation for the inability of the newborn to limit blood flow when perfusion pressure is raised.Key words: retinal vascular responses, prostaglandins, thromboxane, PGE2 receptor subtypes.

Prostaglandin E2-induced interleukin-6 release by a human airway epithelial cell line

2001 ◽  
Vol 280 (1) ◽  
pp. L127-L133 ◽  
Author(s):  
S. Tavakoli ◽  
M. J. Cowan ◽  
T. Benfield ◽  
C. Logun ◽  
J. H. Shelhamer
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Airway Epithelial Cell ◽  
Epithelial Cell Line ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Airway Epithelial ◽  
Human Airway ◽  
Human Airway Epithelial Cell ◽  
Cell Release

Human airway epithelial cell release of interleukin (IL)-6 in response to lipid mediators was studied in an airway cell line (BEAS-2B). Prostaglandin (PG) E2(10−7M) treatment caused an increase in IL-6 release at 2, 4, 8, and 24 h. IL-6 release into the culture medium at 24 h was 3,396 ± 306 vs. 1,051 ± 154 pg/ml (PGE2-treated cells vs. control cells). PGE2(10−7to 10−10M) induced a dose-related increase in IL-6 release at 24 h. PGF2α(10−6M) treatment caused a similar effect to that of PGE2(10−7M). PGE2analogs with relative selectivity for PGE2receptor subtypes were studied. Sulprostone, a selective agonist for the EP-3 receptor subtype had no effect on IL-6 release. 11-Deoxy-16,16-dimethyl-PGE2, an EP-2/4 agonist, and 17-phenyl trinor PGE2, an agonist selective for the EP-1 > EP-3 receptor subtype (10−6to 10−8M), caused dose-dependent increases in IL-6 release. 8-Bromo-cAMP treatment resulted in dose-related increases in IL-6 release. RT-PCR of BEAS-2B cell mRNA demonstrated mRNA for EP-1, EP-2, and EP-4 receptors. After PGE2treatment, increases in IL-6 mRNA were noted at 4 and 18 h. Therefore, PGE2increases airway epithelial cell IL-6 production and release.

Blocking properties of terguride at the 5-HT2 receptor subtypes mediating cardiovascular responses in the rat

2020 ◽  
Vol 98 (8) ◽  
pp. 511-521
Author(s):  
Oscar Alcántara-Vázquez ◽  
Ma. Trinidad Villamil-Hernández ◽  
Araceli Sánchez-López ◽  
Heinz H. Pertz ◽  
Carlos M. Villalón ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Diastolic Blood Pressure ◽  
Receptor Agonist ◽  
Cardiovascular Responses ◽  
Receptor Subtypes ◽  
Pithed Rats ◽  
Anaesthetized Rats ◽  
Dose Dependent

In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT2A/2B receptors. This study has now investigated terguride’s blocking properties on central/peripheral 5-HT2 receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.v. administration of several compounds. In both groups of rats, i.v. bolus injections of 5-HT or (±)-DOI (a 5-HT2 receptor agonist; 1–1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and heart rate. These responses were dose-dependently antagonized by terguride (10–3000 μg/kg). In anaesthetized rats, i.v. bolus injections of BW723C86 (a 5-HT2B receptor agonist; 1–1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and not dose-dependent increases in heart rate, while in pithed rats, these responses were attenuated. The vasopressor responses elicited by BW723C86 in anaesthetized rats were dose-dependently blocked by terguride (10–300 μg/kg), whereas its the tachycardic responses were dose-independently blocked. These results, taken together, suggest that terguride behaved as an antagonist at the 5-HT2 receptors located in the central nervous system and (or) the systemic vasculature. This is the first evidence demonstrating that terguride can block central/peripheral 5-HT2 receptors mediating cardiovascular responses in anaesthetized or pithed rats.

Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

1998 ◽  
Vol 275 (6) ◽  
pp. R2035-R2042 ◽  
Author(s):  
Karie E. Scrogin ◽  
Alan Kim Johnson ◽  
Herbert A. Schmid
Keyword(s):  
Receptor Agonist ◽  
Brain Slice ◽  
Subfornical Organ ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Excitatory Responses ◽  
Rat Brain Slice ◽  
Dose Dependent ◽  
Multiple Receptor ◽  
Serotonergic Innervation

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1–100 μM) with either an increase ( n = 15) or decrease ( n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1–10 μM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 μM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di- n-propylamino)tetralin (8-OH-DPAT; 1–10 μM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

scholarly journals Activation of the NPY Y5 receptor regulates both feeding and energy expenditure

1999 ◽  
Vol 277 (5) ◽  
pp. R1428-R1434 ◽  
Author(s):  
Joyce J. Hwa ◽  
Melanie B. Witten ◽  
Patricia Williams ◽  
Lorraine Ghibaudi ◽  
Jun Gao ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Interscapular Brown Adipose Tissue ◽  
Peptide Analogs ◽  
Brown Adipose ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Intracerebroventricular (ICV) administration of neuropeptide Y (NPY) has been shown to decrease energy expenditure, induce hypothermia, and stimulate food intake. Recent evidence has suggested that the Y5 receptor may be a significant mediator of NPY-stimulated feeding. The present study attempts to further characterize the role of NPY Y5-receptor subtypes in feeding and energy expenditure regulation. Satiated Long-Evans rats with temperature transponders implanted in the interscapular brown adipose tissue (BAT) displayed a dose-dependent decrease in BAT temperature and an increase in food intake after ICV infusion of NPY. Similar effects were induced by ICV administration of peptide analogs of NPY that activate the Y5 receptor, but not by analogs that activate Y1, Y2, or Y4 receptors. Furthermore, ICV infusion of the Y5 selective agonistd-[Trp32]-NPY significantly reduced oxygen consumption and energy expenditure of rats as measured by indirect calorimetry. These data suggest that the NPY Y5-receptor subtype not only mediates the feeding response of NPY but also contributes to brown fat temperature and energy expenditure regulation.

Effects of a Novel Selective Agonist for Prostaglandin Receptor Subtype EP4on Hyperalgesia and Inflammation in Monoarthritic Model

2002 ◽  
Vol 97 (1) ◽  
pp. 170-176 ◽  
Author(s):  
Keiichi Omote ◽  
Tomoyuki Kawamata ◽  
Yoshito Nakayama ◽  
Hiroki Yamamoto ◽  
Mikito Kawamata ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Thermal Hyperalgesia ◽  
Contralateral Side ◽  
Mechanical Hyperalgesia ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Inflammatory Reactions ◽  
Prostaglandin Receptor ◽  
Potential Strategy ◽  
Dose Dependent

Background Cytokines have crucial role in the development and maintenance of inflammation and pain in arthritis. Activation of prostaglandin receptor subtype EP(4) suppresses cytokine production in immune cells. The purpose of this study was to evaluate whether a novel EP(4) agonist would be able to suppress thermal and mechanical hyperalgesia and paw swelling in acute and chronic phases in rat monoarthritic model. Methods Monoarthritis was induced by an injection of complete Freund's adjuvant (CFA) intracapsularly into the tibiotarsal joint of the rats. Withdrawal latencies to thermal stimulation on the hind paw, withdrawal thresholds to mechanical stimulation, paw volume, and ankle diameter were measured 24 h and 4 weeks after the CFA injection. A novel selective EP(4) receptor agonist, ONO-AE1-329 (10, 25, or 50 microg) or saline was administered intracapsularly into the joint. Results Withdrawal latencies and withdrawal thresholds were significantly (P < 0.05) shortened and decreased, respectively, on the arthritic side but not on the contralateral side 24 h and 4 weeks after the CFA injection. In addition, significant (P < 0.05) increases in paw volume and ankle diameter on the arthritic side were observed. Intracapsularly administered ONO-AE1-329 showed significant (P < 0.05) inhibition of thermal and mechanical hyperalgesia and significant (P < 0.05) decrease in paw volume and ankle diameter in a dose-dependent manner at 24 h and 4 weeks after CFA. Conclusion Intracapsular administration of EP(4) receptor agonist effectively inhibited mechanical and thermal hyperalgesia and inflammatory reactions in acute and chronic monoarthritis. An EP(4) agonist would be a potential strategy for inflammatory pain in arthritis.

scholarly journals Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro

2008 ◽  
Vol 42 (1) ◽  
pp. 47-56 ◽  
Author(s):  
C de Bruin ◽  
R A Feelders ◽  
A M Waaijers ◽  
P M van Koetsveld ◽  
D M Sprij-Mooij ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Tt Cells ◽  
A Minor ◽  
Dose Dependent ◽  
Corticotroph Adenomas ◽  
Analogue Octreotide

Dopamine agonists (DA) and somatostatin (SS) analogues have been proposed in the treatment of ACTH-producing neuro-endocrine tumours that cause Cushing's syndrome. Inversely, glucocorticoids (GCs) can differentially influence DA receptor D2 or SS receptor subtype (sst) expression in rodent models. If this also occurs in human neuro-endocrine cells, then cortisol-lowering therapy could directly affect the expression of these target receptors. In this study, we investigated the effects of the GC dexamethasone (DEX) on D2 and sst expression in three human neuro-endocrine cell lines: BON (carcinoid) and TT (medullary thyroid carcinoma) versus DMS (small cell lung cancer), which is severely GC resistant. In BON and TT, sst2 mRNA was strongly down-regulated in a dose-dependent manner (IC50 0.84 nM and 0.16 nM), whereas sst5 and especially D2 were much more resistant to DEX treatment. Sst2 down-regulation was abrogated by a GC receptor antagonist and reversible in time upon GC withdrawal. At the protein level, DEX also induced a decrease in the total number of SS (−52%) and sst2-specific (−42%) binding sites. Pretreatment with DEX abrogated calcitonin inhibition by sst2-preferring analogue octreotide in TT. In DMS, DEX did not cause significant changes in the expression of these receptor subtypes. In conclusion, we show that GCs selectively down-regulate sst2, but not D2 and only to a minor degree sst5 in human neuro-endocrine BON and TT cells. This mechanism may also be responsible for the low expression of sst2 in corticotroph adenomas and underwrite the current interest in sst5 and D2 as possible therapeutic targets for a medical treatment of Cushing's disease.

Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes

2005 ◽  
Vol 93 (3) ◽  
pp. 1145-1157 ◽  
Author(s):  
Zixiu Xiang ◽  
Lie Wang ◽  
Stephen T. Kitai
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Driving Forces ◽  
Brain Slices ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Membrane Excitability

The subthalamic nucleus (STN) is considered to be one of the driving forces in the basal ganglia circuit. The STN is innervated by serotonergic afferents from the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We investigated the effects of 5-HT and 5-HT receptor subtype agonists and antagonists on the firing properties of STN neurons in rat brain slices. We used cell-attached, perforated-patch, and whole cell recording techniques to detect changes in firing frequency and pattern and electrical membrane properties. Due to the depolarization of membrane potential caused by reduced potassium conductance, 5-HT (10 μM) increased the firing frequency of STN neurons without changing their firing pattern. Cadmium failed to occlude the effect of 5-HT on firing frequency. 5-HT had no effect on afterhyperpolarization current. These results indicated that the 5-HT action was not mediated by high-voltage–activated calcium channel currents and calcium-dependent potassium currents. 5-HT had no effect on hyperpolarization-activated cation current ( IH) amplitude and voltage-dependence of IH activation, suggesting that IH was not involved in 5-HT–induced excitation. The increased firing by 5-HT was mimicked by 5-HT2/4 receptor agonist α-methyl-5-HT and was partially mimicked by 5-HT2 receptor agonist DOI or 5-HT4 receptor agonist cisapride. The 5-HT action was partially reversed by 5-HT4 receptor antagonist SB 23597-190, 5-HT2 receptor antagonist ketanserin, and 5-HT2C receptor antagonist RS 102221. Our data indicate that 5-HT has significant ability to modulate membrane excitability in STN neurons; modulation is accomplished by decreasing potassium conductance by activating 5-HT4 and 5-HT2C receptors.

Differential Distribution of 5Ht1D-and 5HT1B-Immunoreactivity within the Human Trigemino-Cerebrovascular System: Implications for the Discovery of New Antimigraine Drugs

Cephalalgia ◽  
1997 ◽  
Vol 17 (8) ◽  
pp. 833-842 ◽  
Author(s):  
J Longmore ◽  
D Shaw ◽  
D Smith ◽  
R Hopkins ◽  
G McAlliste ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Receptor Agonist ◽  
Sensory System ◽  
Receptor Protein ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Therapeutic Action ◽  
Differential Distribution ◽  
Antimigraine Drugs ◽  
Cerebrovascular System

Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.

scholarly journals Adenosine A2A and A2B receptors are both required for adenosine A1 receptor-mediated cardioprotection

2011 ◽  
Vol 301 (3) ◽  
pp. H1183-H1189 ◽  
Author(s):  
Enbo Zhan ◽  
Victoria J. McIntosh ◽  
Robert D. Lasley
Keyword(s):  
Receptor Agonist ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Beneficial Effects ◽  
A1 Receptor ◽  
Developed Pressure ◽  
Adenosine A2a

All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A2A and/or A2B receptors modulate adenosine A1 receptor-mediated cardioprotection. Isolated perfused hearts of wild-type (WT), A2A knockout (KO), and A2BKO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 ± 4% vs. 44 ± 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 ± 2% with CHA vs. 52 ± 5% in control) in WT hearts, effects that were blocked by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A2A receptor agonist CGS-21680 (200 nM) and the A2B agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A2A or A2B receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A2A and A2B receptors are required for adenosine A1 receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes.

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