Elevation of cAMP facilitates noradrenergic transmission in submucous neurons of guinea pig ileum

1993 ◽  
Vol 264 (3) ◽  
pp. G442-G446 ◽  
Author(s):  
D. H. Zafirov ◽  
H. J. Cooke ◽  
J. D. Wood
Keyword(s):  
Guinea Pig ◽  
Ganglion Cells ◽  
Phosphodiesterase Inhibitor ◽  
Input Resistance ◽  
Guinea Pig Ileum ◽  
Synaptic Excitation ◽  
Before And After ◽  
Intracellular Microelectrodes

Slow synaptic excitation and inhibition were studied with intracellular microelectrodes in submucous ganglion cells of the guinea pig ileum. Elevation of adenosine 3',5'-cyclic monophosphate (cAMP) after application of forskolin or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) resulted in slowly activating depolarization of the membrane potential. The depolarization was associated with increased input resistance, enhanced excitability, and suppression of hyperpolarizing afterpotentials. This occurred in AH/type 2 but not S/type 1 neurons. The action of forskolin or IBMX mimicked slow synaptic excitation in the same neurons. Focal electrical stimulation also evoked slow inhibitory postsynaptic potentials (IPSPs). The amplitude and duration of the IPSPs were increased by forskolin or a membrane-permeant analogue of cAMP. Treatment with phentolamine, yohimbine or idazoxan suppressed the IPSPs before and after potentiation by forskolin, suggesting that the IPSPs were mediated by release of norepinephrine acting at alpha 2-adrenoceptors. Application of adenosine or selective adenosinergic A1 agonists suppressed or abolished the IPSPs. The results suggest that elevation of cAMP facilitates the release of norepinephrine at alpha 2-synapses on submucous neurons of guinea pig small bowel.

Synaptic transmission in submucosal ganglia of guinea pig distal colon

1991 ◽  
Vol 260 (6) ◽  
pp. G842-G849 ◽  
Author(s):  
T. Frieling ◽  
H. J. Cooke ◽  
J. D. Wood
Keyword(s):  
Guinea Pig ◽  
Ganglion Cells ◽  
Input Resistance ◽  
Distal Colon ◽  
Presynaptic Muscarinic Receptors ◽  
The Neural Networks ◽  
Type 3 ◽  
Prolonged Response

Intracellular electrical recording was used to investigate synaptic behavior of ganglion cells in the neural networks of the submucosal plexus of the guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs), mediated by nicotinic receptors, were found in all S/type 1 neurons, 70% of AH/type 2, 75% of type 3, and 95% of type 4 neurons. Slow EPSPs were characterized by membrane depolarization, increased input resistance, enhanced action potential discharge, and suppression of hyperpolarizing afterpotentials in 64% of the S/type 1 neurons, 74% of AH/type 2, 31% of type 3, and 70% of type 4 neurons. Micropressure application of acetylcholine evoked a two-component depolarizing response consisting of an initial transient with decreased input resistance followed by a prolonged depolarization associated with increased input resistance. The transient response was suppressed by nicotinic-blocking drugs. Muscarinic antagonists suppressed the prolonged response. Acetylcholine acted also at presynaptic muscarinic receptors to suppress stimulus-evoked fast EPSPs. No stimulus-evoked inhibitory synaptic potentials were observed. Norepinephrine, applied by microejection, acted at alpha 2-adrenoceptors to hyperpolarize the membrane potential in association with decreased neuronal input resistance.

Effects of PACAP on morphologically identified myenteric neurons in guinea pig small bowel

1993 ◽  
Vol 264 (3) ◽  
pp. G414-G421 ◽  
Author(s):  
F. L. Christofi ◽  
J. D. Wood
Keyword(s):  
Small Bowel ◽  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Glial Cells ◽  
Input Resistance ◽  
Myenteric Neurons ◽  
Adenosine Receptor Agonist ◽  
Excitatory Responses

Intracellular microelectrodes were used to examine the actions of pituitary adenylate cyclase-activating peptide (PACAP) on morphologically identified myenteric neurons and glial cells of the guinea pig small bowel. PACAP-27 and PACAP-38 evoked excitatory responses in 96% of after hyperpolarizing (AH)/type 2 neurons. The half-maximal concentration for PACAP-27 was 1.5 nM. The responses consisted of membrane depolarization in association with increased input resistance, suppression of hyperpolarizing afterpotentials, and repetitive spike discharge. Forskolin mimicked the action of PACAP in all AH/type 2 neurons. PACAP excited 36% of S/type 1 neurons. Most of the AH/type 2 neurons had Dogiel II morphology, whereas the S/type 1 neurons were uniaxonal with morphology characteristics of Dogiel I or filamentous neurons. No glial cells responded to PACAP. A selective A1 adenosine receptor agonist blocked the excitatory action of PACAP, and this was reversed by a selective A1 antagonist. The results suggest that excitatory PACAP receptors and inhibitory adenosine A1 receptors are linked to adenylate cyclase in AH/type 2 myenteric neurons.

Histamine receptors on submucous neurons in guinea pig colon

1993 ◽  
Vol 264 (1) ◽  
pp. G74-G80 ◽  
Author(s):  
T. Frieling ◽  
H. J. Cooke ◽  
J. D. Wood
Keyword(s):  
Guinea Pig ◽  
Action Potentials ◽  
Acetylcholine Release ◽  
Input Resistance ◽  
Distal Colon ◽  
Intracellular Microelectrodes ◽  
Selective Agonists ◽  
Nicotinic Synapses

Intracellular microelectrodes were used to investigate the actions of histamine in the submucous plexus of the distal colon of the guinea pig. Three effects resulted from application of histamine to submucous neurons. The first was membrane depolarization associated with increased input resistance and augmented excitability. The second was presynaptic suppression of acetylcholine release at nicotinic synapses. The third occurred during long-term application and consisted of recurrent trains of action potentials associated with periodic depolarization of membrane potential. Pharmacological analysis, with selective agonists and antagonists, suggested mediation of the first and third response by postsynaptic histamine H2 receptors. The second response was mediated by presynaptic histamine H3 receptors. These actions of histamine represent a mechanism for neuroimmune signaling between mucosal mast cells and submucous neurons in gastrointestinal type 1 hypersensitivity reactions to allergens.

Electrophysiological properties of neurons in submucosal ganglia of guinea pig distal colon

1991 ◽  
Vol 260 (6) ◽  
pp. G835-G841 ◽  
Author(s):  
T. Frieling ◽  
H. J. Cooke ◽  
J. D. Wood
Keyword(s):  
Guinea Pig ◽  
Ganglion Cells ◽  
Distal Colon ◽  
Submucosal Plexus ◽  
Electrophysiological Properties ◽  
Small Intestinal ◽  
Type 3

Intracellular recording methods were used in vitro to study the electrophysiological behavior of neurons in ganglia of the submucosal plexus in the distal colon of the guinea pig. The results revealed subpopulations of submucosal ganglion cells that corresponded to the AH/type 2, S/type 1, type 3, and type 4 subpopulations found elsewhere in the intestine. Electrical behavior of colonic submucosal neurons differed from the myenteric plexus of the colon, rectum, and stomach and the small intestinal submucosal plexus mainly in the relative proportions of the different subpopulations. Regional differences in this respect may be a reflection of functional specialization in the diverse regions of the alimentary canal.

Transmural fluxes of 5-hydroxytryptamine in guinea pig ileum

1983 ◽  
Vol 244 (4) ◽  
pp. G421-G425 ◽  
Author(s):  
H. J. Cooke ◽  
M. Montakhab ◽  
P. R. Wade ◽  
J. D. Wood
Keyword(s):  
Guinea Pig ◽  
Ganglion Cells ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Linear Functions ◽  
Guinea Pig Ileum ◽  
Serotonergic Receptors ◽  
Flat Sheet ◽  
Muscularis Externa

Transmural movement of 5-hydroxytryptamine (5-HT) was studied in guinea pig small intestine in vitro in order to test the hypothesis that there is mucosal 5-HT barrier in this species. Segments of guinea pig ileum were mounted as flat sheets in flux chambers or were everted and perfused. Mucosal-to-serosal (Jm leads to s) and serosal-to-mucosal (Js leads to m) fluxes of 5-HT were measured in the absence of 5-HT gradients and under open- or short-circuited conditions. The results indicated that substantial transmural movement of 5-HT occurred in these preparations. Both Jm leads to s and Js leads to m were linear functions of the 5-HT concentration over a range of 1-30 microM and were not significantly different in the two directions. Addition of 2,4-dinitrophenol to both sides of the tissue reduced short-circuit current to zero and increased both tissue conductance and unidirectional 5-HT fluxes. These results suggested that the 5-HT fluxes across the guinea pig ileum occurred by passive mechanisms. Fluxes of 5-HT across preparations with the muscularis externa removed were not significantly different from fluxes across intact preparations. Mucosal-to-serosal 5-HT fluxes in everted perfused sacs were comparable with fluxes in the flat-sheet preparations. The data are not consistent with the hypothesis of a "tissue barrier" that functions to prevent 5-HT from reaching serotonergic receptors on enteric ganglion cells or enteroendocrine cells.

scholarly journals Factors Associated with the Remission of Type 1 Diastolic Dysfunction after Dapagliflozin Treatment in Patients with Type 2 Diabetes

2020 ◽  
Vol 9 (11) ◽  
pp. 3779
Author(s):  
Adina Braha ◽  
Alin Albai ◽  
Romulus Timar ◽  
Laura Diaconu ◽  
Lucian Vasiluță ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diastolic Dysfunction ◽  
Liver Stiffness ◽  
Initial Stiffness ◽  
Reduced Ejection Fraction ◽  
Before And After ◽  
Background Therapy ◽  
One Year

Patients with type 2 diabetes (T2DM) are at high risk of developing cardiovascular disease and heart failure (HF), both with preserved and reduced ejection fraction of the left ventricle. Previous research demonstrated that dapagliflozin treatment is associated with the remission of type 1 diastolic dysfunction (DD1) in patients with T2DM. The main aim of this study was to evaluate the possible baseline predictors associated with the remission of DD1 in patients with T2D after one year of dapagliflozin treatment. In this prospective and observational study, 45 patients with T2DM were evaluated before and after one year of treatment with 10 mg dapagliflozin daily added to their background therapy. In the studied group, 73.3% (33/45) of the patients had DD1 at baseline. The primary outcome of this research was DD1 remission. DD1 remission was associated with improvement of liver stiffness, an increase in estimated glomerular filtration rate (eGFR), and a decrease in hemoglobin A1c (HbA1c). Independent predictors for the remission of DD1 were a more than 0.4 kPa difference in the initial stiffness score and the 1-year assessment fibrosis score and a duration of diabetes ≤8 years. Age, body mass index (BMI), or patient weight after one year did not influence the DD1 outcome. Patients with a T2DM duration of less than eight years have the additional benefit of DD1 remission associated with dapagliflozin treatment beyond the conventional benefits such as improvements in glycemic control, cardiovascular, renal, and hepatic risk reductions. In patients with T2DM, the remission of DD1 was associated with decrease of liver stiffness.

Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats

1997 ◽  
Vol 273 (2) ◽  
pp. R833-R837 ◽  
Author(s):  
Y. H. Wang ◽  
Y. Tache ◽  
A. B. Sheibel ◽  
V. L. Go ◽  
J. Y. Wei
Keyword(s):  
Inhibitory Effect ◽  
Vagal Afferents ◽  
Neural Signals ◽  
Excitatory Effect ◽  
Leptin Sensitivity ◽  
Before And After ◽  
Afferent Terminals

In vitro gastric vagal afferents' (GVAs) unit activities were recorded from the ventral GVA nerve strands in rats. The responsiveness of 16 GVA terminals to close intra-arterial injection of vehicle (0.1 ml), leptin (350 pmol), and cholecystokinin (CCK)-8 (10 pmol) was analyzed to generate a spike count-versus-time histogram. Data of 5-min spike counts before and after each treatment were normalized by dividing the latter by the former. A quotient (Q) > 1 indicates an excitatory effect, Q < 1 indicates an inhibitory effect, and Q close to 1 indicates no effect. Two types of GVA terminals were identified. Type 1 (n = 8) responded to leptin with Q > 1; CCK-8 pretreatment did not consistently alter leptin sensitivity. In contrast, Type 2 (n = 8) responded to leptin with Q < 1 or close to 1, and CCK-8 pretreatment increased the leptin sensitivity so that the terminals responded to subsequent leptin with Q > 1. These data suggest that Type 1 and Type 2 GVA terminals may provide afferent neural signals, which, in turn, will be involved in body weight and food intake control systems, respectively.

Effects of the inflammatory mediator prostaglandin D2 on submucosal neurons and secretion in guinea pig colon

1994 ◽  
Vol 266 (1) ◽  
pp. G132-G139 ◽  
Author(s):  
T. Frieling ◽  
C. Rupprecht ◽  
A. B. Kroese ◽  
M. Schemann
Keyword(s):  
Guinea Pig ◽  
Ganglion Cells ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Prostaglandin D2 ◽  
Flux Chamber ◽  
Dose Dependent Increase ◽  
Dose Dependent

Conventional flux chamber and intracellular recording methods were used to investigate the mode of action of prostaglandin D2 (PGD2) on ion transport in muscle-stripped segments of guinea pig colon and on colonic submucosal ganglion cells. Application of PGD2 resulted in a dose-dependent increase in short-circuit current that was reduced by serosal addition of bumetanide, tetrodotoxin, atropine, or piroxicam, but not hexamethonium. Application of PGD2 to submucosal neurons evoked a depolarization of the membrane potential that was associated with an enhanced spike discharge. In AH/type 2 neurons, postspike afterhyperpolarizations were reduced in amplitude and duration. The depolarizing responses to PGD2 were not affected by tetrodotoxin, indicative of a direct effect of PGD2 on the impaled neurons. Whereas fast excitatory postsynaptic potentials (EPSPs) were not affected by PGD2, slow EPSPs were reduced by a presynaptic effect, indicating presynaptic suppression of noncholinergic neurotransmitter release. The study demonstrates that PGD2 acts as a neuromodulator to evoke nerve-mediated chloride secretion, predominantly through activation of cholinergic submucosal neurons. The results further indicate that PGD2 released from lamina propria immune cells during antigenic stimulation may influence mucosal function by altering electrical behavior of submucosal neurons.

scholarly journals Protein phosphatase composition in the smooth muscle of guinea-pig ileum studied with okadaic acid and inhibitor 2

1989 ◽  
Vol 262 (2) ◽  
pp. 617-623 ◽  
Author(s):  
A Takai ◽  
M Troschka ◽  
G Mieskes ◽  
A V Somlyo
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Okadaic Acid ◽  
Total Activity ◽  
Guinea Pig Ileum ◽  
Control Activity ◽  
Triton X ◽  
Type 1 Phosphatase ◽  
Intracellular Structure

Using okadaic acid, a potent inhibitor of type 2A and type 1 protein phosphatases, and inhibitor 2, an intrinsic inhibitory factor of type 1 phosphatase, we characterized the phosphorylated myosin light-chain (PMLC) phosphatase activity in the smooth-muscle extracts of guinea-pig ileum. In the intact fibres the control activity was 254 +/- 13 nmol of Pi/min per g wet wt. (n = 15) against 32P-labelled PMLC (4 microM) from chicken gizzard. The following phosphatase fractions were identified: an inhibitor-2-sensitive (type 1) fraction (fractional activity = 35%), a Mg2+-dependent and okadaic acid-insensitive (type 2C) fraction (17%), and two type 2A-like fractions that had different susceptibility to okadaic acid. The type 2A-like fraction with lower affinity to okadaic acid accounted for 30% of the control activity. After the cell membrane was permeabilized by Triton X-100, more than 60% of this fraction remained and accounted for about 90% of the total activity, whereas the other fractions were nearly abolished. The type 2A-like fraction may be bound to some intracellular structure such as contractile proteins.

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