Neuroeffector System Research Articles

Ultrastructural changes in early Wallerian degeneration of the neuroeffector system of the rat vas deferens

Ultrastructural changes in early Wallerian degeneration of the neuroeffector system of the rat vas deferens

Evidence that neuropeptide Y and norepinephrine mediate electrical field-stimulated vasoconstriction of rabbit middle cerebral artery.

We investigated the contractile response of isolated rabbit middle cerebral artery (MCA) segments to electrical field stimulation (EFS). The dynamics of the EFS contraction were compared with a similar-sized branch of rabbit ear artery. In comparison with the ear artery, the EFS contractions of the MCA displayed a longer latency and a higher stimulus frequency threshold. Greater stimulation train lengths were required to attain equilibrium, and the time course of EFS response--including force development, plateau, and return to rest tension--was significantly slower than in the ear artery. Morphological and pharmacological studies of the MCA showed that it receives sympathetic adrenergic innervation: whole-mount preparations displayed catecholamine histofluorescence; electron micrographs of MCA sections revealed a population of varicosities containing chromaffin positive large and small vesicles; and EFS contractions were blocked by tetrodotoxin (30 nM) and guanethidine (5 microM) and by chronic surgical sympathectomy. Exposure to prazosin (10 microM) or phenoxybenzamine (1 microM) blocked norepinephrine contractions but did not significantly influence the EFS contraction. Procedures and drugs that antagonized the responses to neuropeptide Y, serotonin, or histamine were also ineffective in blocking the EFS contraction. The involvement of ATP could not be assessed, since the purinergic P2 agonist alpha,beta-methylene ATP was ineffective in blocking ATP-mediated contractions. The EFS contraction, however, could be blocked by a combination of neuropeptide Y desensitization and phenoxybenzamine (30 nM) or prazosin (0.1 microM). These results suggest that norepinephrine and neuropeptide Y are released from sympathetic nerves and mediate EFS contraction by occupation of postjunctional alpha-adrenoceptor and neuropeptide Y receptors. Since the blockade of only one of these components does not diminish the response to EFS, the adrenergic neuroeffector system in this artery may involve complex prejunctional regulatory mechanisms.

Influence of Perivascular Adipose Tissue on Rat Aortic Smooth Muscle Responsiveness

Virtually every blood vessel in the body is surrounded to some degree by adipose tissue. A potential role for perivascular adipose tissue as a neurohumoral regulator of vascular responsiveness was studied. Thoracic aortae obtained from male Sprague-Dawley rats were cut into rings for use in a standard in vitro smooth muscle bath set-up. The vessels were either cleaned of surrounding adipose tissue or left intact. Contractile responses to KCl and phenylephrine as well as relaxation responses to acetylcholine, isoproterenol and sodium nitroprusside were not different between cleaned and intact tissues. However, a significant decrease in the sensitivity to norepinephrine was observed in intact vessels. This altered response was corrected by prior treatment with desipramine plus deoxycorticosterone. Contractile responses of aortic ring preparations to tyramine and a potassium-free physiological solution were significantly greater in intact tissues. Electrical stimulation resulted in no response in cleaned tissues, however, a frequency-dependent contraction was elicited in intact vessels. Phentolamine blocked the contractile responses generated by these manipulations which activate the sympathetic neuroeffector system. Responses evoked by electrical stimulation in intact vascular preparations were significantly attenuated by prior exposure to the selective angiotensin II (AII) antagonist SarI-Ile8-AII. These observations demonstrate that perivascular adipose tissue significantly influences vascular responsiveness in the in vitro setting.

Nitric oxide mediates non-adrenergic non-cholinergic relaxation in some neuroeffector systems: examples of nitrergic transmission

Nitric oxide mediates non-adrenergic non-cholinergic relaxation in some neuroeffector systems: examples of nitrergic transmission

The role of neuroeffector systems in myocardial ischaemia, reperfusion and preservation

The role of neuroeffector systems in myocardial ischaemia, reperfusion and preservation

The influence of in vitro sodium and potassium ion ratio on teleost melanosome intracellular motility

The miniature neuroeffector system represented by the melanophore and neural elements of winter flounder (Pseudopleuronectes americanus) scale slips demonstrates asymmetrical sensitivity to progressive in vitro changes in the relative concentrations of Na+ and K+ ions induce melanosome aggregation more readily than Na+ ions evoke melanosome dispersion, reflecting the influence of K+ induced depolarization on neurotransmitter release.

A new analysis of in vitro Na + and K + induction of teleost melanosome movements

1. The dermal melanophore and sympathetic neural elements of scale slips plucked from Pseudopleuronectes americanus constitute a miniature in vitro neuroeffector system, 2. Phentolamine treatment confirms that K + induction of melanosome aggregation in this species is neurotransmitter mediated, whilst ouabain treatment demonstrates that Na + induced melanosome dispersion is Na +, K +-ATPase dependent in these preparations. 3. Simultaneous ouabain-phentolamine treatment demonstrates that K +and Na + induction of melanosome movements reflect neuronal membrane polarity changes which regulate neurotransmitter release. 4. It is also concluded that melanophore membrane polarity change is not essential in transduction of neurotransmitter signal to melanosome motility.

Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue

To investigate the role of cholinergic neurotransmission in erection, human penile corpus cavernosum tissue was studied. Electrical stimulation of strips of corpus cavernosum suspended in an organ chamber induced contractions and relaxations that were blocked by tetrodotoxin. The contractions also were blocked by bretylium and prazosin. Norepinephrine and phenylephrine contracted the isolated strips and this response was prevented by prazosin. Electrical stimulation-induced relaxations were enhanced by bretylium and physostigmine and partially blocked by atropine. The effect of atropine, but not that of physostigmine, was prevented by bretylium. Corporal strips contracted with norepinephrine relaxed to acetylcholine; this effect was blocked by atropine and enhanced by physostigmine. Strips lacking endothelium contracted normally with norepinephrine, but the relaxation caused by acetylcholine was virtually abolished. Thus endothelium lining the lacunar spaces within human corpus cavernosum is required for the relaxation caused by exogenous acetylcholine. There may be three neurotransmitter effector systems that control corpus cavernosum smooth muscle tone: adrenergic (excitatory), cholinergic (inhibitory), and nonadrenergic noncholinergic (inhibitory). Cholinergic nerves do not dilate or constrict directly the smooth muscle but may modulate other neuroeffector systems and/or the endothelium.

Local Control of Penile Erection: Nerves, Smooth Muscle, and Endothelium

This article reviews the state of knowledge on the neurologic and non-neurologic mechanisms that control the tone of the corpus cavernosum trabecular smooth muscle and the smooth muscles of penile arteries and veins. It includes discussion of the role of the adrenergic, the cholinergic, and the nonadrenergic noncholinergic neuroeffector systems as well as the potential role of the vascular endothelium and prostaglandins in the control of penile erection.

Potential future developments in the field of antihypertensive drugs.

Since an understanding of the pathogenesis of essential hypertension is unlikely to be imminent, there is little chance that antihypertensive therapy will become curative in the near future. What progress can be expected in symptomatic therapy? In the past, nearly all major mechanisms involved in the regulation of blood pressure have become targets of antihypertensive drugs; they include the sympathetic neuro-effector system, neuronal substrates of central cardiovascular regulation, the kidney, the renin angiotensin aldosterone system and the vascular smooth muscle cell. Among drugs that influence the function of the sympathetic nervous system, the clinical potential of one mechanism of action has not yet been explored: it is the inhibition of noradrenaline release through stimulation of inhibitory receptors located at the adrenergic nerve terminals of the cardiovascular system (inhibitory presynaptic receptors). Among the multiple presynaptic receptors, dopamine receptors appear to be a particularly interesting target. The not entirely expected activity of angiotensin converting enzyme (ACE) inhibitors in essential hypertension prompted the search for renin inhibitors. Whether interruption of the cascade of the renin angiotensin system at the first reaction step by renin inhibitors, as compared to the interference at the second step by ACE inhibitors, will yield relevant progress in antihypertensive drug therapy remains to be seen.

Sympathetic control of cerebral arteries: specialization in receptor type, reserve, affinity, and distribution

The sympathetic neuroeffector system in the mammalian cerebral circulation has a number of distinctive features that reflect its specialized role in this vascular bed: 1) there is limited alpha-adrenoceptor-mediated contraction in large vessels that becomes progressively less important with branching; 2) contraction is limited by receptor number; small branches often seem to have no functional alpha adrenoceptors; 3) adrenoceptor affinity for norepinephrine is low and so is sensitivity; and 4) the dominant alpha-adrenoceptor subtype differs in different species and may have unique characteristics in some. There is a mechanism of non-alpha-adrenoceptor-mediated contraction involving low-affinity receptor sites--extraceptors--activated by sympathetic nerves. The pig has a seemingly atypical sympathetic mechanism. On the basis of current information the sympathetic neuroeffector mechanisms of the rabbit seem most clearly related to the human. The size, pattern, and distribution of sympathetic control suggest that the role of the sympathetic nerves is to protect the smaller pial arteries against the consequences of sudden increases in sympathetic adrenal discharge. It is not an important mechanism of controlling cerebral blood flow.

Neurobiology of the intestinal mucosa

The importance of the enteric nervous system for coordinating and programming the digestive modes of the gastrointestinal effecters is well recognized. Attention has been focused in the past on the involvement of intrinsic nerves in generating specific motility patterns of the smooth muscle effecters, with little regard for the influence of intrinsic nerves on mucosal transport processes. The advent of immunohistochemical techniques for identifying neuronal types and their projections has documented the intrinsic innervation of the mucosa and has renewed interest in the epithelium as a neuroeffector system. The first definitive evidence of the direct involvement of the enteric nervous system in the regulation of intestinal mucosal ion transport was provided by Hubel (1) who adapted conventional electrical field stimulation techniques that were used routinely to examine the neural regulation of smooth muscle contractile activity to whole-thickness sheets of intestine in Ussing chambers. This technique, with its subsequent modifications by Cooke et al. (2), has been the basis for current understanding of the involvement of the enteric nervous system in the regulation of mucosal transport function. Significant progress has been made over the last decade to develop the foundation on which to build a working model of neural mechanisms that influence the mucosa; however, physiologic experiments have not kept pace with the morphologic studies that have identified a multiplicity of putative neurotransmitters within submucosa neurons, and, therefore, the

Pharmacology of the erectile tissue of the canine penis

To assess the role of different neuroeffector systems in penile erection, pharmacological agents were tested in vitro using strips of corpus cavernosum tissue from the dog. Alpha-adrenoceptor agonists, K + or histamine caused concentration-dependent contraction. Tyramine caused a poorly sustained contraction, as did nicotine in some cases. In precontracted preparations, relaxation was caused by beta 2-adrenoceptor or muscarinic cholinoceptor agonists, or by vasoactive intestinal peptide. The results suggest that a noradrenergic alpha-adrenoceptor system maintains penile flaccidity in the dog. Penile erection may result from the activation of inhibitory beta 2-adrenergic, muscarinic and/or peptidergic systems.

Inhibition of acetylcholinesterase accelerates axon terminal withdrawal at the developing rat neuromuscular junction.

In developing skeletal muscles, the rate at which superfluous innervation is lost from the endplates depends on the general level of neuromuscular activity. Whether it is activity of the presynaptic or postsynaptic structures (or both) that is critical is not well established. In this work, we transitorily inhibited the AChE of soleus muscle in postnatal rats, in order to increase postsynaptic activity, without directly altering activity of the nerve terminals. We then followed the time course of disappearance of axon terminals from the endplates of treated and normal muscles, using electron-microscope techniques. Three hours after inhibition of AChE, the muscle fibres exhibited local supercontracture and ultrastructural damage in the region of the endplate, consistent with local elevation of Ca2+ levels. At the same time, small electron-opaque vesicles, apparently of muscular origin, appeared in the synaptic cleft. The nerve terminals, however, were entirely normal in number and appearance. One day after treatment, endplates of esterase-inhibited muscles showed accelerated loss of nerve terminals, compared to endplates of normally developing muscles. No further loss of nerve terminals occurred, once AChE activity returned at the endplate. These results suggest that the rate at which superfluous nerve terminals retract from the developing neuromuscular junction is regulated by the level of activation of the muscle. It seems likely that activity of postsynaptic sites may similarly regulate changes in innervation patterns, in other developing or adapting neuro-neuronal or neuro-effector systems.

Actions of Ptychodiscus brevis toxins on nerve and muscle membranes

C. H. Wu, J. M. C. Huang, S. M. Vogel, V. Scruggs Luke, W. D. Atchison and T. Narahashi. Actions of Ptychodiscus brevis toxins on nerve and muscle membranes. Toxicon 23, 481 – 487, 1985 — Pharmacological actions of two brevetoxins isolated from Ptychodiscus brevis, T17 and T34, on nerve and muscle membranes were studied using vertebrate and invertebrate preparations. T17 (10 ng/ml) caused an increase in the frequency of miniature endplate potentials (MEPPs) in rat and frog neuromuscular junctions. Application of tetrodotoxin (TTX) completely abolished the increase in MEPP frequency. The results suggest that T17 depolarizes the nerve terminal through opening of the sodium channel. Application of either T17 or T34 to the crayfish and squid giant axons caused a dose-dependent depolarization of the axon membranes with a maximum depolarization of about 30 mV. The depolarizing action was antagonized by sodium-free external saline solution or TTX. Voltage clamp experiments demonstrated that the primary action of the toxins is to cause the sodium channels to open at the normal resting potential. The binding of toxin to a channel site could be prevented by procaine, but not by TTX. The binding site for T17 is presumably separate from the TTX receptor, but related or identical to the binding site for procaine. The brevetoxin-induced depolarization of the nerve terminal membrane with the subsequent enhanced transmitter release is the underlying mechanism for a number of pharmacological actions on various neuro-effector systems.

Neurogenic and Myogenic Responses in Isolated Smooth Muscle of The Bovine Teat

Strips of bovine teat smooth muscle were studied. Their innervation was investigated with analytical pharmacology on field stimulated preparations. The content of noradrenaline in the teat wall and the sphincter region was determined. The main results were: teat smooth muscle has properties of single unit smooth muscle i.e. automaticity and active response to stretch. Especially the sphincter region is inclined to rapid phasic rhythmicity. The teat smooth muscle receives excitatory adrenergic innervation. The noradrenaline released from the nerves preferentially activates α-adrenoceptors, while β-adrenoceptors essentially are noninnervated and humoral. The sphincter region has a higher concentration of noradrenaline and a more intimate neuro-effector arrangement. This is probably of functional significance. Moderate chilling increases the response to adrenergic nerve stimulation while it is decreased at higher temperatures. This has most likely physiological importance. The results are discussed with respect to in vivo findings and it is concluded that the bovine teat smooth muscle with its excitatory adrenergic nerves forms a normally very efficient neuro-effector system with a particular strength in the sphincter around the streak canal.

Relation between functional maturation of cervical sympathetic innervation and ontogeny of α-noradrenergic smooth muscle contraction in the rat

The functional ontogeny of a sympathetic neuroeffector system consisting of postganglionic neuron and smooth muscle end organ was studied in vivo in the rat at selected times from birth through 75 days of age. The maximum noradrenergic contractile response of the smooth muscle (Mu¨ller's) component of the levator palpebrae was assessed with the directly acting agonist, methoxamine. The functional capacity of the nerve terminals innervating the muscle to evoke contraction was determined by displacing their endogenous noradrenaline with tyramine. The integrity of the pathway from preganglionic axon to end organ was tested by stimulating the preganglionic axons electrically. The smooth muscle contractile response to methoxamine increased in a step-wise fashion through the 20th postnatal day. On day 1, the response was 2% of the mature (70–75 day) value. The response increased to 17% on day 4, and remained at this level through the 9th day. A second increase to 32% occurred between the 10th and 12th day, and there was no further increase through the 19th day. Responses increased to 64% of the mature value by the 45–50th postnatal day. Responses to tyramine were always comparable to those evoked by methoxamine. Electrical stimulation of the preganglionic nerve failed to evoke contractions on days 1 and 4, but from day 8 on, responses to preganglionic stimulation, tyramine and methoxamine were comparable. Decentralization of the superior cervical ganglion on the 1st postnatal day decreased the response to endogenously-released nerve terminal noradrenaline by 25% at 18–19 days postnatally and the deficit persisted to maturity. In contrast, the response to direct noradrenergic stimulation was attenuated at 70–75 days postnatally, but not at 18–19 and 45–50 days. Sham operation itself significantly decreased responses to methoxamine and tyramine at 18–19 and 45–50 days of age, but not at 70–75 days. The following conclusions were reached. Functional capacity of the postganglionic sympathetic nerve terminals develops at least as rapidly as the capacity of the smooth muscle to respond directly to α-noradrenergic stimulation. The connection between central nervous system and postganglionic sympathetic neuron is not required to initiate functional maturation of the neuron, postsynaptic α-noradrenergic receptors or post-receptor smooth muscle contractile elements. After ganglionic neurotransmission is established, there is a significant, though modest, transynaptically mediated contribution to overall functional maturation of postganglionic neuron and end organ. The maturational deficit (about 25%) which follows decentralization of the postganglionic neuron on the 1st postnatal day is manifest first in the sympathetic nerve terminal; this, in turn, appears to lead to a deficit in smooth muscle response to direct α-noradrenergic stimulation. Thus, decentralization in the neonate prior to establishment of ganglionic neurotransmission leads to subsensitivity of α-noradrenergic end organ response while decentralization in mature animals is known to result in supersensitivity. Since the contribution of neural, transynaptic factors to maturation was modest in this sympathetic neuroeffector system, consideration is given to the possibility that humoral factors such as thyroid and growth hormone play major roles in development of the postganglionic neuron and end organ.

Adrenergic mechanisms in canine intralobar pulmonary arteries and veins.

The responses of canine intralobar pulmonary arteries (IPA) and veins (IPV) to transmural nerve stimulation (TNS), and exogenously administered norepinephrine (NE) were studied to evaluate the alpha-adrenergic neuroeffector system in the canine pulmonary vasculature. IPA and IPV elicited contractions in response to both NE (10(-10) to 10(-5) M) and TNS (0.5-32 Hz, 2 ms duration and delay). The equilibrium (steady state) contractile responses of IPA and IPV to TNS were abolished with the adrenergic neuronal blocking agents guanethidine and bretylium and the depolarization blocking agent tetrodotoxin in concentrations which did not affect the responses to NE or KCl. The contractile responses of IPA and IPV to TNS and NE were reduced in a concentration-dependent way, by the alpha-adrenergic receptor-blocking agents phentolamine, tolazoline and clonidine. The contractile responses of IPA and IPV to TNS and NE were enhanced after inhibition of neuronal reuptake of NE (uptake1) with cocaine, as well as after blockade of extraneuronal reuptake of NE (uptake2) with hydrocortisone. Analysis of the equilibrium responses of the IPA and IPV to TNS and NE with an Arunlakshana-Schild plot to define the concentration of alpha 1-receptor antagonists necessary to double the ED50 for TNS and NE (defined as the pA2), demonstrated that the postsynaptic alpha-receptors of IPV differed from that of IPA. These data support the conclusions that IPA and IPV 1) contain a functional adrenergic innervation and neuroeffector system, 2) contract in response to both TNS and NE, 3) demonstrate the presence of mechanisms for both uptake1 and uptake2 of NE, and 4) IPV contain postsynaptic alpha-receptors that may differ from each other.

Neuronal mechanisms for bilateral coordination of salivary gland activity in Helisoma.

The salivary neuroeffector system of Helisoma consists of the paired salivary glands and buccal ganglia. Previous work demonstrated that neuronal control was required for coordination of activity in the two salivary glands. This neuronal control is provided by a pair of identified buccal ganglion neurons, 4R and 4L. This study examines the organization of this neuronal control and addresses the questions of monosynaptic vs. polysynaptic pathways as well as the bilateral effects of each neuron 4. Action potentials in neuron 4 elicit one-for-one EPSPs in a subpopulation of the salivary cells. These EPSPs can, in some cases, be increased by TEA injection into a neuron 4 and are unaffected by the addition of six-times normal calcium. These data coupled with the constancy of synaptic transmission, as well as morphological evidence, further indicate the monosynaptic nature of the connection between neurons 4 and salivary secretory cells. Three different mechanisms exist to insure that activity in 4R and 4L result in coordinated activation of the salivary glands: (1) Lucifer Yellow injection and direct intracellular recording and stimulation demonstrate that both 4R and 4L can send axons to and innervate both salivary glands; (2) both 4R and 4L receive virtually identical synaptic input from higher-order buccal ganglion neurons; and (3) 4R and 4L are electrically coupled. Thus, the system is organized with a high degree of redundancy, and bilateral synchrony of glandular activity is assured by mechanisms at various levels of neuronal organization.

A cellular analysis of chromatophore patterning in winter flounder ( Pseudopleuronectes americanus walbaum)

Abstract o 1. Integumentary patterns in Pseudopleuronectes americanus can be resolved into dark band, pale iridophore spot and general background components in which dermal and epidermal melanophores, xanthophores and iridophores are distributed. 2. Patterning can be attributed partly to differences in chromatophore densities between the three components. 3. The pattern components are characterized by different capacities for rapid aggregation and dispersion of melanosomes, suggesting the existence of three distinct melanophore neuroeffector systems. 4. Behaviour of the xanthophores suggests relatively strong control of their pigment dispersion and weak control of their aggregation with differences in regulatory balance between pattern components.