Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neuroeffector Junction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2000

Neural integration and allergic disease.

Changes in neural activity play a key role in many symptoms of allergic disease, including sneezing, coughing, itching, and ocular irritation, among others. The mechanisms underlying allergen-induced changes in neural activity (reflexes) are largely unknown and under active investigation. Allergic inflammation can affect neural activity on a variety of levels, including at the primary afferent sensory nerve, integrative centers of the central nervous system, autonomic ganglia, and autonomic neuroeffector junction. At the level of the afferent sensory nerve, mediators released after allergen exposure either directly or indirectly increase neuronal firing. At the level of sensory ganglia, which contain cell bodies that innervate a variety of organs, changes in neuronal excitability may lead to a generalization of allergic symptoms. In the central nervous system, where afferent inputs from throughout the body converge, allergic inflammation may be associated with central sensitization, leading to the modulation of the neural reflexes. Finally, at the autonomic ganglia and neuroeffector junction, allergic inflammation appears to be associated with enhanced ganglionic transmission and neurotransmitter release, respectively. Mechanisms by which allergen challenge affects neuronal activity at various levels of the nervous system are reviewed, with a primary emphasis on studies of airway physiologic factors.

Central Nervous System↗
PubMed1981

George E. Brown memorial lecture. Local modulation of adrenergic neurotransmission.

The cardiovascular reflexes, by regulating the traffic in the sympathetic nerves, govern the amount of norepinephrine released from the nerve endings. However, the final adjustments in the amount of neurotransmitter available to activate the beta 1 receptors in the heart and the alpha receptors in the blood vessels take place at the sympathetic neuroeffector junction. Thus, a decrease in pH, hyperosmolarity, moderate increases in the concentration of K+ ion, adenosine and adenine nucleotides depress the release of norepinephrine at any given level of sympathetic nerve activity. These metabolic changes, which occur in active tissues, and in particular in adenosine, have been proposed as mediators of the accompanying local hyperemia. In addition, they apparently facilitate this local dilatation by disconnecting the blood vessels in the active tissues from sympathetic control. Acetylcholine, histamine and 5-hydroxytryptamine are present in and around certain blood vessels and can activate specific receptors on the prejunctional fibers and cause vasodilatation by reducing the output of neutrotransmitter. Some of the norepinephrine released into the synaptic cleft may depress its continued release by activating prejunctional alpha receptors. In contrast, angiotensin II, by a local action on the nerve endings, can augment the release of transmitter. Decreases in local temperature reduce transmitter release but augment the affinity of the postjunctional alpha receptors for norepinephrine. The role of these local events at the neuroeffector junction, their physiologic significance and potential clinical importance are discussed in this review.

Acetylcholine↗
PubMed1988

Cardiovascular effects and modulation of noradrenergic neurotransmission following central and peripheral administration of neuropeptide Y.

Experiments have been conducted to evaluate the effect of neuropeptide Y (NPY) administered at three distinct levels of the nervous system: 1) the posterior hypothalamic nucleus, 2) the spinal cord, and 3) the vascular noradrenergic neuroeffector junction. It was observed that NPY produced varying cardiovascular effects at these three distinct sites of the nervous system. Microinjections into the posterior hypothalamic nucleus resulted in an increase in blood pressure, which was reduced by prior microinjection of a muscarinic or H1-histamine antagonist but not an H2-histamine antagonist. In addition to the involvement of histaminergic and cholinergic pathways, the pressor effect of NPY appears to result from an increase in sympathetic outflow. NPY was also seen to decrease the potassium-induced release of norepinephrine (NE) from slices obtained from the posterior hypothalamic nucleus. In contrast to what was observed in the hypothalamus, the intrathecal injection of NPY at a level of T4 or T10 in anesthetized or T10 in unanesthetized rats resulted in a depressor effect as well as a decrease in heart rate. Both an alpha 2- and beta-adrenoceptor antagonist reduced the NPY effect. The depressor effect of intrathecal NPY was attenuated in rats pretreated with reserpine as well as in Spontaneously Hypertensive rats (SHR). These data suggest that the effects of NPY are closely associated with sympathetic preganglionic neurons in the spinal cord. At the vascular noradrenergic neuroeffector junction, NPY decreased the nerve stimulation-induced release of NE while potentiating the contractile response. Moreover, NPY potentiated the increase in perfusion pressure of the perfused mesenteric arterial bed in response to angiotensin, vasopressin, or phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Disruption of iris adrenergic transmission as an index of poor endorphin modulation in headache.

Pupillometry was used to evaluate the effect of oral or topically applied adrenomimetic drugs and of local morphine on pupillary size in headache patients and controls. In headache sufferers, a disruption of adrenergic transmission is suggested since the iris adrenergic nerve terminal is apparently poor in NE; this neuron also exhibits a reduced capacity of neurotransmitter synthesis and an adrenoceptor hypersensitivity. The spontaneous reduction of pupillary size detected in headache sufferers also suggests a decreased sympathetic input. The miosis, registered after conjunctival instillation of morphine, demonstrates that iris is a possible example of an opioid-dependent adrenergic neuron in man. A poor modulation of the iris adrenergic transmission induces, in headache sufferers, a neuronal incontinence and therefore a chronic intrasynaptic leakage of NE, resulting in an exhausted empty neuron on the one hand and a compensatory hyperactivity of the effector muscular cell on the other. Since indirect evidence suggests a morphine modulation of the iris adrenergic neuron, a deficiency of endorphin modulation could be the mechanism of disruption of iris adrenergic transmission. Apart from the theoretical aspects, the exploration of iris neuroeffector junction represents a noninvasive an simple diagnostic tool in headache.

Endorphins↗
PubMed1976

Inhibition of neuromuscular transmission by prostaglandin E1 in the circular muscle of the guinea-pig vas deferens.

Pressure increases elicited by contractions of the circular muscle of the isolated guinea-pig vas deferens in response to nerve stimulation were recorded. In contrast to longitudinal muscle which contracted in response to 1--50 pulses, circular muscle responded only to longer trains of pulses (10--500) at a frequency of 10 Hz. Atropine (1.4 muM) caused a slight depression of responses to 100 shocks. Phentolamine at a concentration of 2.6 muM failed to inhibit the response to stimulation, but a higher concentration (53 muM) caused a definite blockade. Guanethidine (25 muM) strongly reduced the responses. With a stimulus train of 100 pulses no inhibition by prostaglandin E1 (PGE1) (0.028 muM) could be demonstrated; however, at a lower number of shocks (20--50) a clearcut depression was observed. The lower the number of pulses the more marked was the depression. The observation that PGE1 failed to block the contractions evoked by noradrenaline (59 muM) suggests a presynaptic inhibitory action of the prostaglandin. It is suggested that noradrenaline is the transmitter in both muscle coats of the guinea-pig vas deferens and that the neuroeffector junctions are sensitive to the effect of PGE1.

Animals↗
PubMed1991

Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor.

1. The action of analogues and C-terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CA1 of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition. 2. Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the post-synaptic CA1 pyramidal neurones, indicating their action is at a presynaptic site. 3. The full-sequence analogues, peptide YY (PYY) and human NPY (hNPY), were equipotent with NPY at the presynaptic receptor, while desamido hNPY was without activity. 4. NPY2-36 was equipotent with NPY. Fragments as short as NPY 13-36 were active, but gradually lost activity with decreasing length. NPY 16-36 had no effect on extracellular field potentials, but still significantly inhibited excitatory postsynaptic potential amplitudes. Fragments shorter than NPY 16-36 had no measurable effect on synaptic transmission. 5. The presynaptic NPY receptor in hippocampal CA1 therefore shares an identical agonist profile with the presynaptic Y2 receptor at the peripheral sympathetic neuroeffector junction.

Action Potentials↗
PubMed1986

Estimation of intrasynaptic norepinephrine concentrations in humans.

Levels of synaptic cleft norepinephrine associated with pressor responses were estimated in humans by measuring blood pressure and arterial plasma norepinephrine during norepinephrine infusion and during yohimbine-induced release of endogenous norepinephrine. Linear pressor response-log norepinephrine concentration relationships were observed during the infusions. At a pressor response of 20 mm Hg, arterial norepinephrine averaged 3647 pg/ml. The pressor-log norepinephrine relationship was shifted more than fivefold to the left during combined ganglionic, alpha 2-adrenergic receptor, and Uptake1 (neuronal norepinephrine uptake) blockade: arterial norepinephrine averaged 684 pg/ml at a 20 mm Hg pressor response. During yohimbine-induced release of endogenous norepinephrine in desipramine-pretreated subjects, arterial norepinephrine averaged 467 pg/ml at a 20 mm Hg pressor response. Since the norepinephrine concentration in the synaptic clefts must have been between the values for plasma norepinephrine during its infusion and during its endogenous release, we estimated that in healthy people, a 20 mm Hg sympathetically mediated pressor response is associated with about a 560 pg/ml (3.3 nM) concentration of norepinephrine in the average neuroeffector junction.

Adult↗
PubMed1988

Differences in norepinephrine dynamics in large and small pulmonary arteries of dog.

These studies address the apparent dissociation between the amounts of norepinephrine (NE) released from small and large pulmonary arteries of dogs by a standard electrical stimulus and the contractile tensions that developed in these tissues. Segments of vessels were studied in organ baths or in a superfusion apparatus during electrical stimulation. Endogenous NE was quantitated using liquid chromatography with electrochemical detection. 'Release' of NE was studied under conditions in which uptakes of NE from the synaptic cleft were impaired, and overflow of NE was studied when these uptakes were operative. 'Release' of NE was predictably greater than overflow in all arteries. In the large pulmonary artery, greater contractile tensions were measured when greater amounts of NE were present in superfusate. In the small pulmonary artery, contractile tensions did not directly correlate with the amounts of NE measured in the superfusate. These studies indicate that NE dynamics are different at neuroeffector junctions in large and small pulmonary arteries. Several explanations to account for these differences are discussed.

Animals↗
PubMed1972

Peristalsis in the rabbit distal colon.

1. The motility of the distal colon of the rabbit has been examined by the conventional Trendelenburg method and by an isometric, isovolumic modification of this method.2. The colon shows a range of movements, and tetrodotoxin and cold-storage have been used in an attempt to differentiate between myogenic and neurally integrated activities.3. The observable myogenic movements are pendulum movements, ;tone rings' and ;tone waves'; the last of these can be weakly propulsive. The rabbit colon also shows a neurally organized and powerfully propulsive movement which corresponds to the peristaltic wave.4. The implication of a role for nervous structures in the propulsive activity of the rabbit distal colon is at variance with the view of Lee (1960).5. The myenteric reflex arc in the colon has been examined pharmacologically. Cholinergic neural transmission has been implicated at the ganglionic-synaptic and neuroeffector junctions, but additional noncholinergic mechanisms of chemical transmission have not been excluded.

Acetylcholine↗
PubMed1999

Extended angiotensin converting enzyme inhibition changes the innervation of renal glomerular afferent arterioles.

Chronic inhibition of the angiotensin I converting enzyme (ACE) with enalapril, results in a phenotypic change of the medial cells of renal afferent arterioles from contractile smooth muscle cells to renin containing epithelioid cells. In normal animals, the density of the innervation of the juxtaglomerular renin containing epithelioid cells is much lower compared to the contractile cells. The effector tissues are known to play an important role in determining the pattern and density of their innervation. In this study, we tested the hypothesis that the density of the innervation of the afferent arteriole smooth muscle cells decreases when they change their phenotype from contractile to renin containing epithelioid cells. The results show that the density of the innervation had significantly increased and the association of the terminals with the smooth muscle cells had changed. There were significantly more varicosities around renal afferent arterioles from rabbits treated with enalapril (10 microg/kg/h) for 6 weeks (mean +/- SEM = 634 +/- 175 x 10(3)/mm2 vessel surface, cf. 329 +/- 69 x 10(3)/mm2 vessel surface in untreated rabbits, P = 0.05), with the number of neuroeffector junctions remaining the same (124 +/- 14 and 164 +/- 32 x 10(3)/mm2 vessel surface) and significantly more non-contacting varicosities (i.e. lying > 100 nm from the medial cells) (74 +/- 5% and 25 +/- 7%, respectively; P = 0.003). Thus, there was no reduction in the innervation of afferent arterioles in which the smooth muscle cells had changed phenotype in response to enalapril treatment as hypothesised. Instead, it would appear that proliferation of the innervation had occurred, with the formation of additional varicosities but these varicosities failed to form neuromuscular junctions. This study has identified a form of neural plasticity in the kidney that has not previously been described.

Angiotensin I↗
PubMed1968

Mechanisms of reflex vasodilation: assessment of the role of neural reuptake of norepinephrine and release of histamine.

The mechanisms of reflex vasodilation were studied in an innervated canine hindlimb preparation which was perfused at a constant rate. Reflex vasodilation was produced by suddenly increasing the pressure in the trunk by the intravenous injection of norepinephrine, with consequent stimulation of the baroreceptors. When the basal vasoconstrictor tone exerted by the sympathetic nervous system on the systemic arterial bed was minimized, either by pretreatment with the alpha adrenergic blocking agent phenoxybenzamine or with reserpine, which depletes endogenous catecholamine stores, reflex vasodilation was virtually abolished. Administration of cocaine, a drug which blocks reuptake of norepinephrine by the nerve terminals, significantly reduced reflex vasodilation, the response after cocaine averaging 47% of the vasodilator response in the control period. Cocaine also potentiated the vasoconstriction caused by intra-arterially administered norepinephrine but attenuated the vasoconstriction induced by tyramine. The antihistamine, tripelennamine, had effects similar to those of cocaine. It is suggested, therefore, that reflex vasodilation results from a sudden decrease in the level of norepinephrine at the neuroeffector junction, which is a consequence of the cessation of norepinephrine secretion, together with continued and possibly augmented uptake. When the uptake mechanism is impaired, either by the administration of cocaine or tripelennamine, the magnitude of reflex vasodilation is diminished. It does not appear necessary to postulate active secretion of a vasodilator substance to account for reflex vasodilation.

Animals↗
PubMed1990

Peptides and vasomotor mechanisms.

The multiple and diverse roles played by neuropeptide Y, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide and other biologically active peptides in the cardiovascular system are considered. A model of the vascular neuroeffector junction is described, which illustrates the interactions of peptidergic and nonpeptidergic transmitters that are possible at pre- and postjunctional sites. The effects of peptides on specific endothelial receptors are also described, which highlights the ability of these agents to act as dual regulators of vascular tone at both adventitial and intimal surfaces, following local release from nerves, or from endothelial cells themselves. Changes in expression of vascular neuropeptides that occur during development and aging in some disease situations and following nerve lesion are discussed.

Animals↗
PubMed1986

The effect of age on release of norepinephrine by tyramine from rat heart.

The effect of age on the capacity of tyramine to promote the release of norepinephrine (NE) at the cardiac adrenergic neuroeffector junction was investigated in isolated hearts of rats, 6, 12 and 24 months of age. Hearts were perfused by the method of Langendorff and tyramine was administered in increasing doses as a bolus injection. There was no age-related difference in the effect of tyramine on NE release nor on the relationship between the amount of NE released and chronotropic response induced by the released NE. These findings indicate that there is no difference in the effectiveness of tyramine in promoting the release of NE from the tyramine-sensitive pool as a function of age.

Aging↗
PubMed1991

Mathematical model of cellular basis for the respiratory sinus arrhythmia.

The respiratory sinus arrhythmia (RSA) is a vagally mediated oscillation in cardiac cycle length at the frequency of breathing. We developed a mathematical model that predicted the temporal and frequency dependence of the RSA. We used the mathematical model to examine the underlying cellular basis for the RSA at the level of the sinus node. We alternated efferent vagal activity between a low and a high frequency at the frequency of breathing. This oscillation caused the rate of acetylcholine (ACh) release to oscillate between a low and a high rate at the frequency of breathing. ACh degradation followed linear pharmacokinetics for physiological concentrations of ACh. Therefore, the concentration of ACh in neuroeffector junctions of the sinus node oscillated at the frequency of breathing. Membrane potential responded rapidly to changes in the concentration of ACh relative to the rate of ACh degradation. Thus, the time course of the RSA depended on the rate of ACh degradation. Membrane potential oscillated at several integer multiples of frequency of breathing and at various higher frequencies, which were integer multiples of the frequency of breathing and the frequencies of firing of the sinus node. However, computing cardiac cycle length from membrane potential eliminated the higher frequencies. Therefore, cardiac cycle length oscillated at several integer multiples of the frequency of breathing, but not at these higher frequencies.

Acetylcholine↗
PubMed1984

Ultrastructure of vesicourethral innervation. II. Postganglionic axoaxonal synapses in intrinsic innervation of the vesicourethral lissosphincter: a new structural and functional concept in micturition.

The interrelationships of postganglionic axons in intrinsic neuroplexuses of the vesicourethral lissosphincter ('internal sphincter') were studied ultrastructurally in the cat and rat of both sexes. Direct axoaxonal contracts between cholinergic and adrenergic axons were common in preterminal axon bundles and at neuroeffector junctions. Similar contacts between 2 cholinergic or 2 adrenergic axons were less frequent. Most contacts were ultrastructurally simple, but some had focal areas of very close axolemmal apposition, and some were focally specialized as bona fide chemical synaptic complexes. The axoaxonal contacts are introduced as a complex interaxonal synaptic system that chemically, and possibly also electrically, modulates neurotransmission in postganglionic axons innervating the lissosphincter, presynaptically (prejunctionally) at the infraganglionic level, especially by reciprocal cholinergic/adrenergic axonal interaction. This synaptic system is introduced as a potential, hitherto unrecognized, site of action of autonomic drugs, and as a key factor in the neural mechanism controlling continent closure of the lissosphincter during bladder filling, its opening to initiate and maintain voiding, and its closure to terminate the micturition cycle.

Animals↗
PubMed1993

Neuropeptide Y modulates the vascular response to periarterial nerve stimulation primarily by a postjunctional action in the isolated perfused rat kidney.

Neuropeptide Y (NPY) is a 36-amino acid peptide that is colocalized and released with norepinephrine (NE) from central and peripheral adrenergic neurons and has been suggested to contribute to the control of vascular tone. This study was undertaken to assess the contribution of NPY at the vascular adrenergic neuroeffector junction in the rat kidney. Experiments were performed in isolated rat kidneys prelabeled with tritiated NE ([3H] NE). Infusion of NPY (1-50 nM) resulted in a dose-dependent increase in basal perfusion pressure and potentiated the vasoconstrictor response elicited by renal nerve stimulation (RNS; 0.5-4 Hz). NPY (10-50 nM) also potentiated the vasoconstrictor response elicited by exogenous NE (150 pmol). These effects of NPY were mimicked by [Leu31,Pro34]NPY, a NPY Y1 receptor agonist whereas [13-36]NPY, a NPY Y2 receptor agonist failed to alter the basal, RNS- or NE-induced increase in perfusion pressure. NPY (10 nM) and [Leu31,Pro34]NPY but not [13-36] NPY inhibited RNS-induced fractional tritium overflow only at high frequencies of stimulation (10 and 16 Hz) without altering basal tritium efflux. Periarterial nerve stimulation at 4 and 10 Hz resulted in release of immunoreactive NPY by 8- and 38-fold, respectively. These data indicate that NPY acts primarily at the postjunctional sites to produce renal vasoconstriction and to potentiate the vasoconstrictor response to RNS via Y1 receptors. Furthermore, NPY coreleased with adrenergic transmitter may also inhibit release of NE at higher frequencies of RNS (8-16 Hz) by acting on Y1 receptors at the prejunctional sites.

Adrenergic Fibers↗
PubMed1993

Altered cardiac adrenergic neurotransmission in streptozotocin-induced diabetic rats.

1. Functional alterations of the sympathetic neuroeffector junction of the left atria were studied in rats with streptozotocin-induced diabetes. 2. Eight to 12 weeks of diabetes resulted in a marked decrease in the positive inotropic response of left atria to electrical field stimulation (EFS). 3. The overflow of [3H]-noradrenaline from diabetic left atria caused by EFS was much less than that from control preparations. 4. The concentration-response curves showed no change in sensitivities of the left atria to exogenous noradrenaline and tyramine in diabetic rats. The maximum positive inotropic response to these agents were similar in diabetic and control animals. 5. The left atrial content of noradrenaline was not significantly changed in diabetic rats. The cocaine-sensitive uptake of [3H]-noradrenaline was also unaltered. 6. Atropine enhanced the positive inotropic response and [3H]-noradrenaline overflow induced by EFS in control left atria. Similarly, yohimbine caused an enhancement of EFS-evoked inotropic response in control atria. However, these effects of the antagonists were not observed in diabetic left atria. 7. It is concluded that the decrease in the positive inotropic response of the left atria to EFS in diabetic rats is caused by an impairment of noradrenaline release from the sympathetic nerve terminals through a calcium-dependent exocytotic mechanism. The present results also indicate that presynaptic alpha 2-adrenoceptors and muscarinic receptors that are linked to inhibition of the noradrenaline release during nerve stimulation may be functionally impaired in diabetic animals.

Animals↗
PubMed1996

Vagal control of sinoatrial rhythm: a mathematical model.

The ionic mechanisms underlying vagal control of the cardiac pacemaker were investigated using a new single cell mathematical model of sinoatrial node electrical activity. The model was formulated from a wide range of electrophysiological data available in the literature, with particular reference to whole cell recordings from enzymatically isolated sinoatrial node cells. Development of the model was prompted by the lack of an existing physiologically accurate formulation of sinoatrial node activity that could reproduce the known complex chronotropic response of the pacemaker to brief-burst vagal stimulation, as observed in whole animal and isolated sinus node preparations. Features of the model include the dynamic modulation of the hyperpolarisation-activated current (i(f)) and the L-type calcium current (iCa,L) by acetylcholine, the improved characterisation of the muscarinic potassium current (iK,ACh), assigning the entire background potassium current (ib,K) to spontaneous openings of its channels, and the utilisation of second order kinetics for acetylcholine within the neuroeffector junction. Simulations performed using brief vagal stimuli elicited a strong hyperpolarisation of the membrane which prolonged the cycle in which it was delivered in a phase-dependent manner. This phase-dependency was presented in the form of a standard phase response curve which was characterised by a positive linear slope region, a breakpoint characteristic and a "no effect" zone in which the vagal pulse could no longer prolong the cycle. The breakpoint was manifested as a discontinuity in the curve which was examined by bracketing this point at the limit of the double precision arithmetic employed. At these boundary points on either side of the breakpoint, the vagal stimulus was able to activate outward iK,ACh in such a manner as to finely balance the increasing inward iCa,L trying to generate phase 0 upstroke. On decay of iK,ACh, the membrane either subsequently repolarised or fired to produce an action potential depending on the precise phase of the stimulus. The positive linear slope portion of the PRC was characterised by a strong resetting type behaviour in which the membrane hyperpolarised to approximately the same value, irrespective of the phase of stimulus delivery. For vagal stimulus bursts applied throughout the "no effect" zone, outward iK,ACh was not sufficiently activated in order to overcome the strong inward drive of iCa,L and could not prevent upstroke occurring. For these vagal stimuli, the subsequent cycle was hyperpolarised and prolonged. The size of the "no effect" zone was directly related to the inherent latency incorporated in the activation characteristic of iK,ACh. In contrast to previous models of vagal pacemaker control, our new model was able to reproduce the classical triphasic chronotropic response to brief vagal stimulation characterised by a primary inhibition response, a postinhibitory rebound and a secondary inhibition response. In particular, the postinhibitory rebound was due to activation of the inward hyperpolarisation-activated current by the vagally-induced membrane hyperpolarisation, whilst the secondary inhibition phase resulted from the inhibition of the hyperpolarisation-activated current by acetylcholine. The model suggests that the complex chronotropic responses of the cardiac pacemaker to brief vagal stimulation arises from inherent ionic mechanisms operating within the sinoatrial node.

Acetylcholine↗