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.

Modulation of Ca2+ transients in neonatal and adult rat cardiomyocytes by angiotensin II and endothelin-1

1996 ◽  
Vol 270 (3) ◽  
pp. H857-H868 ◽  
Author(s):  
R. M. Touyz ◽  
J. Fareh ◽  
G. Thibault ◽  
B. Tolloczko ◽  
R. Lariviere ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Agonist ◽  
Dependent Manner ◽  
Induced Responses ◽  
Ang Ii ◽  
Binding Studies ◽  
Vasoactive Peptides ◽  
Adult Cardiomyocytes ◽  
Etb Receptor ◽  
Dose Dependent

Vasoactive peptides may exert inotropic and chronotropic effects in cardiac muscle by modulating intracellular calcium. This study assesses effects of angiotensin II (ANG II) and endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) in cultured cardiomyocytes from neonatal and adult rats. [Ca2+]i was measured microphotometrically and by digital imaging using fura 2 methodology. Receptor subtypes through which these agonists induce responses were determined pharmacologically and by radioligand binding studies. ANG II and ET-1 increased neonatal atrial and ventricular cell [Ca2+]i transients in a dose-dependent manner. ANG II (10(-11) to 10(-7) M) failed to elicit [Ca2+]i responses in adult cardiomyocytes, whereas ET-1 increased [Ca2+]i in a dose-dependent manner. The ETA receptor antagonist BQ-123 significantly reduced (P 7< 0.05) ET-1 induced responses, and the ETB receptor agonist IRL-1620 (10(-7) to 10(-5) M) significantly increased (P < 0.05) [Ca2+]i in neonatal and adult cardiomyocytes. ET-1 binding studies demonstrated 85% displacement by BQ-123 and approximately 15% by the ETB receptor agonist sarafotoxin S6c, suggesting a predominance of ETA receptors. Competition binding studies for ANG II failed to demonstrate significant binding on adult ventricular myocytes, indicating the absence or presence of very few ANG II receptors. These data demonstrate that ANG II and ET-1 have stimulatory [Ca2+]i effects on neonatal cardiomyocytes, whereas in adult cardiomyocytes, ANG II-induced effects are insignificant, and only ET-1-induced responses, which are mediated predominantly via ETA receptors, are preserved. Cardiomyocyte responses to vasoactive peptides may thus vary with cardiac development.

Subfornical organ efferents to paraventricular nucleus utilize angiotensin as a neurotransmitter

1993 ◽  
Vol 265 (2) ◽  
pp. R302-R309 ◽  
Author(s):  
Z. Li ◽  
A. V. Ferguson
Keyword(s):  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Response Times ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Neural Responses ◽  
Local Pressure ◽  
Electrophysiological Studies ◽  
Excitatory Responses ◽  
Control Stimulation

In this study, we have utilized electrophysiological single unit recordings to evaluate the effects of nonpeptidergic angiotensin II (ANG II) antagonists on neural responses of hypothalamic paraventricular nucleus (PVN) neurons to either electrical stimulation in subfornical organ (SFO) or direct application of ANG II. Electrical stimulation (200-400 microA; 0.1 ms) in the SFO resulted in excitatory responses in 36 of 50 PVN neurons tested. Peristimulus histogram analysis of such excitatory effects demonstrated latencies of < 30 ms and variability of response times of approximately 50 ms in 14 of these 36 neurons. In view of previous anatomic and electrophysiological studies such inputs were therefore considered to be monosynaptically mediated by direct neural inputs from the SFO. The remaining 22 cells excited by such SFO stimulation showed responses of longer latency and duration suggestive of a different underlying synaptic mechanism. Local pressure ejection of ANG II into the PVN resulted in increased neural activity in 50% (9 of 18) of the neurons tested. After systemic (3 mg/kg iv) or local (2 x 10(-2) M; 1-25 s; 2-40 psi) microinjection of the nonpeptidergic angiotensin II1 (AT1) receptor antagonist losartan, SFO excitations were attenuated in 63.9% (23 of 36) of the PVN neurons tested, such pharmacologically blocked excitatory responses being reduced by 68.3 +/- 5.2% from control stimulation effects (P < 0.001). Similar losartan-induced attenuations of both short latency (presumed monosynaptic) (50.0%) and longer latency (72.7%) responses were observed. In addition, losartan also abolished the excitatory effects of local administration of ANG II on 77.8% (7 of 9) of ANG II-sensitive neurons in PVN tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Segmental differences in angiotensin receptor subtypes in interlobular artery of hydronephrotic rat kidneys

1993 ◽  
Vol 265 (6) ◽  
pp. F881-F885 ◽  
Author(s):  
K. Hayashi ◽  
H. Suzuki ◽  
T. Saruta
Keyword(s):  
Vessel Diameter ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Functional Roles ◽  
Renal Vasoconstriction ◽  
Mediated Action ◽  
Renal Microvasculature ◽  
Dose Dependent ◽  
Rat Kidneys ◽  
At2 Receptors

Recent studies demonstrate that angiotensin II (ANG II)-induced vascular action is mediated preferentially by AT1 receptors. Although autoradiographic studies indicate the presence of AT2 receptors in large preglomerular vessels, functional roles for AT2 receptors in ANG II-induced renal vasoconstriction remain undetermined. We examined the effects of DuP-753 and PD-123319 on ANG II-induced vasoconstriction of interlobular arteries (ILA) in isolated perfused hydronephrotic rat kidneys to directly assess the AT1- and AT2-mediated action of ANG II on renal microvessels. Both DuP-753 (0.1-10 microM) and PD-123319 (0.1-10 microM) elicited dose-dependent vasodilation of ANG II-induced ILA constriction, with 86 +/- 4% and 36 +/- 4% inhibition by 10 microM DuP-753 and PD-123319, respectively. The reversal by DuP-753 of ANG II-induced ILA vasoconstriction was greater in small-caliber segments than in large-caliber segments. In contrast, the ability of PD-123319 (10 microM) to inhibit the vasoconstriction was augmented as the vessel diameter increased (slope = +0.46, correlation coefficient = +0.68; P < 0.01). Thus, although AT1 predominantly mediates the ANG II-induced ILA vasoconstriction, PD-123319-sensitive ANG II receptors (e.g., AT2 or AT1B) may also participate partly in the ILA vasoconstriction, particularly at large-caliber segments. In conclusion, distribution of ANG II receptor subtypes may differ depending on the size of the renal microvasculature.

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.

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.

GABAB Receptor Modulation of Rapid Inhibitory and Excitatory Neurotransmission From Subfornical Organ and Other Afferents to Median Preoptic Nucleus Neurons

2004 ◽  
Vol 92 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Miloslav Kolaj ◽  
Donglin Bai ◽  
Leo P. Renaud
Keyword(s):  
Gabab Receptor ◽  
Potassium Conductance ◽  
Subfornical Organ ◽  
Receptor Subtypes ◽  
Preoptic Nucleus ◽  
Paired Pulse ◽  
Median Preoptic Nucleus ◽  
Postsynaptic Currents ◽  
Receptor Modulation ◽  
Rat Brain Slice

Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO). Whole cell patch-clamp recordings in sagittal rat brain slice preparations revealed that 28/40 MnPO neurons responded to electrical stimulation of SFO efferents with bicuculline-sensitive GABAA receptor-mediated inhibition and glutamate-mediated postsynaptic excitation involving AMPA and N-methyl-d-aspartate (NMDA) receptor subtypes, blockable with 2,3-dioxo-6nitro-1, 2,3,4-tetrahydrobenzo [f] quinoxaline-7-sulfoamide disodium (NBQX) and d-2-amino-4-phosphonovaleric acid (d-APV), respectively. Bath applications of baclofen induced a concentration-dependent (0.3–10 μM) reduction in these SFO-evoked postsynaptic currents, attenuation of SFO-evoked paired-pulse depression, and reduction in frequency (but not amplitude) of miniature postsynaptic currents, consistent with an action at presynaptic GABAB receptors. Baclofen's effects on miniature currents lacked sensitivity to barium, ω-conotoxin GVIA, and cadmium. Acting at postsynaptic GABAB receptors, baclofen hyperpolarized a majority of MnPO neurons by increasing a G protein–coupled inwardly rectifying potassium conductance and suppressing an N-type high-voltage–activated calcium conductance. The latter contributed to reduction in action potential afterhyperpolarization and enhanced cell firing and spike frequency adaptation when tested with a depolarizing stimulus. All baclofen-induced effects were blockable with CGP52432 . CGP52432 alone had no significant effect on SFO-evoked postsynaptic current amplitudes or paired-pulse ratios, but did induce an increase in miniature inhibitory postsynaptic current (mIPSC) frequency in 2/4 cells tested, indicating that ambient levels of GABA could activate presynaptic GABAB receptors on undefined inputs. These observations indicate that MnPO neurons receive both a GABAergic and glutamatergic innervation from SFO. Both forms of rapid neurotransmission are subject to modulation via pre- and postsynaptic GABAB receptors.

Neuronal actions of oxytocin on the subfornical organ of male rats

1999 ◽  
Vol 276 (6) ◽  
pp. E1004-E1008 ◽  
Author(s):  
Takayoshi Hosono ◽  
Herbert A. Schmid ◽  
Kazuyuki Kanosue ◽  
Eckhart Simon
Keyword(s):  
Receptor Antagonist ◽  
Subfornical Organ ◽  
Male Rats ◽  
Vasopressin Receptor ◽  
Ang Ii ◽  
Inhibitory Effects ◽  
Extracellular Recordings ◽  
Similar Threshold ◽  
Dose Dependent

The aim of this study was to investigate effects of oxytocin (OT) on electrical neuronal activities in rat subfornical organ (SFO) and compare its action with the well-described excitatory effects of blood-borne angiotensin II (ANG II) on the same SFO neurons. With the use of extracellular recordings from spontaneously active neurons in slice preparations of the SFO of male rats, 11.7% of tested neurons ( n = 206) were excited and 9.7% were inhibited by superfusion with 10−6 M OT. Both excitatory and inhibitory effects of OT were dose dependent with similar threshold concentrations and were blocked by a specific OT-receptor antagonist but not by a vasopressin receptor antagonist. Blocking synaptic transmission with low calcium medium suppressed only inhibitory effects of OT. All but one of the OT-sensitive neurons were also excited by superfusion with ANG II at a concentration much lower than required for OT, suggesting that synaptically released OT rather than blood-borne OT alters the activity of SFO neurons in vivo. The results support the hypothesis that neurally released OT may modulate SFO-mediated functions by acting on OT-sensitive neurons.

scholarly journals Subfornical organ neurons integrate cardiovascular and metabolic signals

2017 ◽  
Vol 312 (2) ◽  
pp. R253-R262 ◽  
Author(s):  
Nicole M. Cancelliere ◽  
Alastair V. Ferguson
Keyword(s):  
Patch Clamp ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Metabolic Homeostasis ◽  
Circumventricular Organ ◽  
Autonomic Functions ◽  
Bath Application ◽  
Metabolic Signal ◽  
Metabolic Hormone

The subfornical organ (SFO) is a critical circumventricular organ involved in the control of cardiovascular and metabolic homeostasis. Despite the plethora of circulating signals continuously sensed by the SFO, studies investigating how these signals are integrated are lacking. In this study, we use patch-clamp techniques to investigate how the traditionally classified “cardiovascular” hormone ANG II, “metabolic” hormone CCK and “metabolic” signal glucose interact and are integrated in the SFO. Sequential bath application of CCK (10 nM) and ANG (10 nM) onto dissociated SFO neurons revealed that 63% of responsive SFO neurons depolarized to both CCK and ANG; 25% depolarized to ANG only; and 12% hyperpolarized to CCK only. We next investigated the effects of glucose by incubating and recording neurons in either hypoglycemic, normoglycemic, or hyperglycemic conditions and comparing the proportions of responses to ANG ( n = 55) or CCK ( n = 83) application in each condition. A hyperglycemic environment was associated with a larger proportion of depolarizing responses to ANG ( χ2, P < 0.05), and a smaller proportion of depolarizing responses along with a larger proportion of hyperpolarizing responses to CCK ( χ2, P < 0.01). Our data demonstrate that SFO neurons excited by CCK are also excited by ANG and that glucose environment affects the responsiveness of neurons to both of these hormones, highlighting the ability of SFO neurons to integrate multiple metabolic and cardiovascular signals. These findings have important implications for this structure’s role in the control of various autonomic functions during hyperglycemia.

23. A new adult rat brain slice preparation for ex vivo NMR spectroscopy studies of stroke

1994 ◽  
Vol 52 (1) ◽  
pp. A11
Author(s):  
M.T. Espanol ◽  
L. Litt ◽  
L.-H. Chang ◽  
T.L. James ◽  
P.R. Weinstein ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Rat Brain ◽  
Brain Slice ◽  
Ex Vivo ◽  
Slice Preparation ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Spectroscopy Studies ◽  
Rat Brain Slice ◽  
Brain Slice Preparation
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