Presynaptic modulation of acetylcholine release from cardiac parasympathetic neurons

1985 ◽  
Vol 248 (1) ◽  
pp. H33-H39 ◽  
Author(s):  
G. T. Wetzel ◽  
J. H. Brown
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptor ◽  
Acetylcholine Release ◽  
Electrical Field Stimulation ◽  
Inhibitory Effect ◽  
Muscarinic Agonist ◽  
Parasympathetic Nerve ◽  
Presynaptic Modulation ◽  
Rat Atria ◽  
Alpha Adrenergic Receptors

Acetylcholine can be released from parasympathetic nerve endings in rat atria by 57 mM K+ depolarization or by electrical field stimulation. We have studied the presynaptic modulation of [3H]acetylcholine release from superfused rat atria prelabeled with [3H]choline. Exogenous acetylcholine and the specific muscarinic agonist oxotremorine inhibit the stimulation-induced overflow of [3H]acetylcholine into the superfusion medium. The half-maximal inhibitory concentration (IC50) of oxotremorine is 0.3 microM. The cholinesterase inhibitor neostigmine also decreases K+-stimulated [3H]acetylcholine overflow, whereas the muscarinic antagonist atropine enhances the overflow of [3H]acetylcholine. These data suggest that acetylcholine release in atria is modulated through negative feedback by the endogenous transmitter. The sympathetic adrenergic neurotransmitter norepinephrine and the neurohormone epinephrine also inhibit the overflow of [3H]acetylcholine by approximately 60%. The IC50 values for the inhibitory effects of these catecholamines are 6.3 and 2.2 microM, respectively. The inhibitory effect of norepinephrine is blocked by the alpha-adrenergic receptor antagonist yohimbine but not by the beta-adrenergic receptor antagonist propranolol. We suggest that presynaptic muscarinic and alpha-adrenergic receptors participate in the physiological and pharmacological control of cardiac parasympathetic activity.

Interaction between prolactin and catecholamines on hypothalamic GnRH release in vitro

1996 ◽  
Vol 151 (2) ◽  
pp. 269-275 ◽  
Author(s):  
A E Calogero ◽  
N Burrello ◽  
A M Ossino ◽  
R F A Weber ◽  
R D'Agata
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Adrenergic Mechanism ◽  
Gnrh Release ◽  
Β Adrenergic Receptors

Abstract Brain catecholamines have been implicated in the regulation of gonadotrophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses the pulsatile release of LH in the rat through a corticotrophin-releasing hormone (CRH)-dependent mechanism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-releasing neurone. Given that PRL stimulates the release of NA from hypothalamic explants and that NA stimulates the release of hypothalamic CRH, we hypothesized that this neurotransmitter may be involved in the intrahypothalamic neuroendocrine circuit mediating the inhibitory effects of PRL on GnRH release. To test this hypothesis, we evaluated the effects of PRL on GnRH release in the presence of α- or β-adrenergic receptor antagonists using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As previously shown, PRL at a concentration of 100 nm inhibited basal iGnRH release by about 35%. Phentolamine, a non-selective α-adrenergic receptor antagonist, prazosin, an α1-receptor antagonist, and yohimbine, an α2-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In contrast, propranolol, a non-selective β-adrenergic receptor antagonist, atenolol, a β1-receptor antagonist, and ICI-118,551, a β2-receptor antagonist, had no effect. None of these compounds had any effect on basal iGnRH release. These findings suggested that an α-adrenergic mechanism is involved in the suppressive effects of PRL on GnRH release. Since the activation of α-adrenergic receptors increases hypothalamic CRH release, we evaluated whether PRL stimulates CRH release via an α-adrenergic mechanism. PRL stimulated basal CRH release by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, α-, but not β-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimental conditions, PRL inhibits GnRH release through an α-adrenergic mechanism which activates the CRH-secreting neurone. Journal of Endocrinology (1996) 151, 269–275

Effects of neurokinin receptor antagonists in virus-infected airways

2000 ◽  
Vol 279 (1) ◽  
pp. L59-L65 ◽  
Author(s):  
David B. Jacoby ◽  
Bethany L. Yost ◽  
Thomas Elwood ◽  
Allison D. Fryer
Keyword(s):  
Electrical Stimulation ◽  
Receptor Antagonist ◽  
Acetylcholine Release ◽  
Parainfluenza Virus ◽  
Muscarinic Agonist ◽  
Receptor Function ◽  
Vagus Nerves ◽  
Neurokinin Receptor ◽  
Neurokinin 1 ◽  
Stimulation Of

We investigated the effects of a neurokinin-1 (NK1) receptor antagonist (SR-140333) and a NK2 receptor antagonist (SR-48968) on airway responsiveness and on the function of neuronal M2 muscarinic receptors, which normally inhibit vagal acetylcholine release, in guinea pigs infected with parainfluenza virus. Antagonists were given 1 h before infection and daily thereafter. Four days later, bronchoconstriction induced by either intravenous histamine (which is partly vagally mediated) or electrical stimulation of the vagus nerves was increased by viral infection compared with control. In addition, the ability of the muscarinic agonist pilocarpine to inhibit vagally induced bronchoconstriction was lost in virus-infected animals, demonstrating loss of neuronal M2 receptor function. Macrophage influx into the lungs was inhibited by pretreatment with both antagonists. However, only the NK1 receptor antagonist prevented M2 receptor dysfunction and inhibited hyperresponsiveness (measured as an increase in either vagally induced or histamine-induced bronchoconstriction). Thus virus-induced M2 receptor dysfunction and hyperresponsiveness are prevented by a NK1 receptor antagonist, but not by a NK2 receptor antagonist, whereas both antagonists had similar anti-inflammatory effects.

Phospholipase C from Clostridium Perfringens Induces Human Platelet Aggregation in Plasma

1988 ◽  
Vol 59 (02) ◽  
pp. 236-239 ◽  
Author(s):  
Giovanna Barzaghi ◽  
Chiara Cerletti ◽  
Giovanni de Gaetano
Keyword(s):  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Phospholipase C ◽  
Clostridium Perfringens ◽  
Human Platelet ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
Thromboxane Receptor Antagonist

SummaryWe studied the aggregating effect of different concentrations of phospholipase C (PLC) (extracted from Clostridium perfringens) on human platelet-rich plasma (PRP). PRP was preincubated with PLC for 3 min at 37° C and the platelet aggregation was followed for 10 min. The threshold aggregating concentration (TAG) of PLC was 3-4 U/ml.We also studied the potentiation of PLC with other stimuli on platelet aggregation. Potentiating stimuli, such as arachidonic acid (AA), ADP. Platelet Activating Factor (PAF) and U-46619 (a stable analogue of cyclic endoperoxides) were all used at subthreshold concentrations. We also studied the possible inhibitory effect of aspirin, apyrase, TMQ, a prostaglandin endoper- oxide/thromboxane receptor antagonist and BN-52021, a PAF receptor antagonist. Only aspirin and apyrase were able to reduce aggregation induced by PLC alone and PLC + AA and PLC + ADP respectively. TMQ and BN-52021 were inactive. In ex vivo experiments oral aspirin (500 mg) partially inhibited platelet aggregation induced by PLC alone, PLC + AA and PLC + ADP 2 and 24 h after administration. Aspirin 20 mg for 7 days also reduced aggregation induced by PLC + AA.

Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic α2-Adrenergic Receptors

2002 ◽  
Vol 87 (4) ◽  
pp. 1938-1947 ◽  
Author(s):  
Yu-Zhen Pan ◽  
De-Pei Li ◽  
Hui-Lin Pan
Keyword(s):  
Receptor Antagonist ◽  
Synaptic Input ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Dorsal Root ◽  
Primary Afferents ◽  
Noradrenergic System ◽  
Analgesic Action ◽  
Adrenergic Agonists ◽  
Excitatory Synaptic Input

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIo neurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIo neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIo neurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIo neurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.

scholarly journals Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Barbara Jana ◽  
Jarosław Całka
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Domestic Animals ◽  
Inhibitory Effect ◽  
Receptor Subtypes ◽  
Beta Adrenergic Receptor ◽  
Pharmacological Modulation ◽  
Uterine Inflammation ◽  
Myometrial Contractility

AbstractUterine inflammation is a very common and serious condition in domestic animals. To development and progression of this pathology often lead disturbances in myometrial contractility. Participation of β1-, β2- and β3-adrenergic receptors (ARs) in noradrenaline (NA)-influenced contractility of the pig inflamed uterus was studied. The gilts of SAL- and E.coli-treated groups were administered saline or E.coli suspension into the uterine horns, respectively. Laparotomy was only done in the CON group. Compared to the period before NA administration, this neurotransmitter reduced the tension, amplitude and frequency in uterine strips of the CON and SAL groups. In the E.coli group, NA decreased the amplitude and frequency, and these parameters were lower than in other groups. In the CON, SAL and E.coli groups, β1- and β3-ARs antagonists in more cases did not significantly change and partly eliminated NA inhibitory effect on amplitude and frequency, as compared to NA action alone. In turn, β2-ARs antagonist completely abolished NA relaxatory effect on these parameters in three groups. Summarizing, NA decreases the contractile amplitude and frequency of pig inflamed uterus via all β-ARs subtypes, however, β2-ARs have the greatest importance. Given this, pharmacological modulation of particular β-ARs subtypes can be used to increase inflamed uterus contractility.

Both M1 and M3 receptors regulate exocrine secretion by mucous acini

1996 ◽  
Vol 271 (6) ◽  
pp. C1963-C1972 ◽  
Author(s):  
D. J. Culp ◽  
W. Luo ◽  
L. A. Richardson ◽  
G. E. Watson ◽  
L. R. Latchney
Keyword(s):  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Muscarinic Agonist ◽  
High Affinity ◽  
Muscarinic Response ◽  
M1 Receptor ◽  
M3 Receptors ◽  
Pharmacological Studies ◽  
Equilibrium Dissociation

We investigated the role of M1 and M3 receptors in regulating exocrine secretion from acini isolated from rat sublingual glands. In secretion experiments, we derived affinity values (KB) from Schild regression analysis for the antagonists pirenzepine (61.0 nM) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM). The KB for 4-DAMP is similar to its affinity value [equilibrium dissociation constant from competition studies (Ki); 1.81 nM] determined from radioligand competition experiments. In contrast, the KB for pirenzepine is between its high-affinity (17.6 nM) and low-affinity (404 nM) Ki values. In separate secretion experiments, we found that the M1 receptor antagonist, M1-toxin, induces a rightward shift in the concentration-response curve to muscarinic agonist and inhibits maximal secretion by 40%. The inhibitory effect of M1-toxin appears specific for M1 receptor blockade, since the toxin abolishes acinar high-affinity pirenzepine-binding sites and does not inhibit secretion induced by nonmuscarinic agents. Additional pharmacological studies indicate muscarinic receptors do not function through putative neural elements within isolated acini. Our combined results are consistent with both M1 and M3 receptors directly regulating mucous acinar exocrine secretion and indicate M3 receptors alone are insufficient to induce a maximal muscarinic response.

Vascular effects of free radicals generated by electrical stimulation

1984 ◽  
Vol 247 (5) ◽  
pp. H709-H714 ◽  
Author(s):  
F. S. Lamb ◽  
R. C. Webb
Keyword(s):  
Electrical Stimulation ◽  
Free Radical ◽  
Experimental System ◽  
Electrical Field Stimulation ◽  
Oxygen Metabolism ◽  
Inhibitory Effect ◽  
Oxygen Free Radical ◽  
Vascular Effects ◽  
Electrical Field ◽  
Rat Tail

Electrical field stimulation (9 V, 1.0 ms, 4 Hz) of isolated segments of rat tail arteries and dog coronary arteries inhibits contractile responses to exogenous norepinephrine and elevated potassium concentration. This inhibitory effect of electrical stimulation is blocked by various agents that alter oxygen metabolism: superoxide dismutase, catalase, glutathione, ascorbate, and dimethyl sulfoxide. The observations suggest that the inhibitory effect is due to an action of oxygen free radical metabolites that are generated by the electrical stimulation of the oxygen-rich buffer. These free radical metabolites have two actions: 1) they oxidize drugs in the experimental system, and 2) they exert a direct inhibitory action on vascular smooth muscle.

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