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N J Dun

Publications and source records attributed to N J Dun.

138 records · Page 8Linked to original sources
PubMed1980

A comparative study of the pharmacological properties of the positive potential recorded from the superior cervical ganglia of several species.

Sucrose gap recording technique was employed to record surface potentials from superior cervical ganglia (SCGs) of several species. Repetitive preganglionic stimulation (30 Hz, 1-2 sec) elicited in curarized rabbit, rat and cat SCGs, a biphasic response as the initial slow positive (P) potential, was followed by a late negative (LN) potential. In curarized guinea-pig SCG, a LN response with no detectable P potential was observed. Neostigmine (0.5-1 microM) increased the amplitude and duration of the P and LN responses in the majority of the rabbit, rat and cat SCGs. LN response of guinea-pig SCG was first enhanced by neostigmine; subsequently, it was converted into a hyperpolarizing potential. Alpha receptor antagonists, phenoxybenzamine, phentolamine and dihydroergotamine, and a beta receptor antagonist, propranolol, did not appreciably alter the P and LN responses of the rabbit, cat and rat SCG or neostigmine-induced hyperpolarization of the guinea-pig SCG. Dopaminergic receptor antagonists, haloperidol, chlorpromazine and metoclopramide, caused no significant depression of the P and LN responses in the rabbit SCG. Atropine (1 microM) consistently abolished the P and/or LN of all these ganglia, as well as the neostigmine-induced hyperpolarization of the guinea-pig SCG. These results demonstrate that muscarinic receptors are involved in the generation of P and LN potentials of mammalian sympathetic ganglia, while the adrenergic and disynaptic nature of P response remains to be clarified. Furthermore, there appears to be no correlation between the generation of P potential and elevation of cyclic AMP in the SCG.

Acetylcholine↗
PubMed1978

Involvement of an interneuron in the generation of the slow inhibitory postsynaptic potential in mammalian sympathetic ganglia.

Acetylcholine (AcCho) was applied electrophoretically to cells of isolated rabbit superior cervical ganglia, and the response was recorded by means of intracellular recording techniques. In the presence of d-tubocurarine (5 micron), AcCho applied by tetanic current pulses elicited three distinct membrane potential changes: a slow depolarization, a slow hyperpolarization, and a biphasic response consisting of an initial hyperpolarization followed by a depolarization. Atropine (1 micron) abolished all the membrane potential changes elicited by AcCho. On the other hand, superfusion with a low-Ca/high-Mg solution, tetrodotoxin (0.1 micron), or haloperidol (0.1 micron) selectively and reversibly blocked AcCho-induced hyperpolarization without appreciably affecting the depolarization. The membrane resistance remained relatively constant during the course of hyperpolarization. Application of steady depolarizing and hyperpolarizing currents decreased and increased, respectively, the amplitude of hyperpolarization. These results demonstrate that the hyperpolarization elicited by AcCho is electrophysiologically and pharmacologically similar to the slow inhibitory postsynaptic potential induced by nerve stimulation; furthermore, they support the view that the slow inhibitory postsynaptic potential elicited by presynaptic stimulation is a disynaptic phenomenon involving the release of a second transmitter, possibly dopamine, from an interneuron.

Acetylcholine↗
PubMed1977

Dopamine and adenosine 3',5'-monophosphate responses of single mammalian sympathetic neurons.

Acetylcholine (ACh), dopamine, and dibutyryl-adenosine 3',5'-monophosphate (dbcAMP) were applied iontophoretically to the rabbit superior cervical ganglion cells from triple-barreled micropipettes, and the response was recorded by intracellular techniques. All ganglion cells tested responded to the depolarizing action of ACh, whereas less than half of the cells that responded to ACh were hyperpolarized by dopamine. This effect was blocked by low concentrations of haloperidol. None of the cells examined responded to dbcAMP applied by iontophoresis. Hence, the present result is not consistent with the concept that a cyclic AMP mechanism underlies the hyperpolarizing effect of dopamine.

Acetylcholine↗
PubMedDate not supplied

Endomorphins: localization, release and action on rat dorsal horn neurons.

Endomorphin (Endo) 1 and 2, two tetrapeptides isolated from the bovine and human brain, have been proposed to be the endogenous ligand for the mu-opiate receptor. A multi-disciplinary study was undertaken to address the issues of localization, release and biological action of Endo with respect to the rat dorsal horn. First, immunohistochemical studies showed that Endo-1- or Endo-2-like immunoreactivity (Endo-1- or Endo-2-LI) is selectively expressed in fiber-like elements occupying the superficial layers of the rat dorsal horn, which also exhibit a high level of mu-opiate receptor immunoreactivity. Second, release of immunoreactive Endo-2-like substances (irEndo) from the in vitro rat spinal cords upon electrical stimulation of dorsal root afferent fibers was detected by the immobilized antibody microprobe technique. The site of release corresponded to laminae I and II where the highest density of Endo-2-LI fibers was localized. Lastly, whole-cell patch clamp recordings from substantia gelatinosa (SG) neurons of rat lumbar spinal cord slices revealed two distinct actions of exogenous Endo-1 and Endo-2: (1) depression of excitatory and/or inhibitory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (2) hyperpolarization of SG neurons. These two effects were prevented by the selective mu-opiate receptor antagonist beta-funaltrexamine. The localization of endomorphin-positive fibers in superficial layers of the dorsal horn and the release of irEndo upon stimulation of dorsal root afferents together with the observation that Endo inhibits the activity of SG neurons by interacting with mu-opiate receptors provide additional support of a role of Endo as the endogenous ligand for the mu-opiate receptor in the rat dorsal horn.

Afferent Pathways↗
PubMedDate not supplied

G protein activation by endomorphins in the mouse periaqueductal gray matter.

The midbrain periaqueductal gray matter (PAG) is an important brain region for the coordination of mu-opioid-induced pharmacological actions. The present study was designed to determine whether newly isolated mu-opioid peptide endomorphins can activate G proteins through mu-opioid receptors in the PAG by monitoring the binding to membranes of the non-hydrolyzable analog of GTP, guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS). An autoradiographic [(35)S]GTPgammaS binding study showed that both endomorphin-1 and -2 produced similar anatomical distributions of activated G proteins in the mouse midbrain region. In the mouse PAG, endomorphin-1 and -2 at concentrations from 0.001 to 10 microM increased [(35)S]GTPgammaS binding in a concentration-dependent manner and reached a maximal stimulation of 74.6+/-3.8 and 72.3+/-4.0%, respectively, at 10 microM. In contrast, the synthetic selective mu-opioid receptor agonist [D-Ala(2),NHPhe(4), Gly-ol]enkephalin (DAMGO) had a much greater efficacy and produced a 112.6+/-5.1% increase of the maximal stimulation. The receptor specificity of endomorphin-stimulated [(35)S]GTPgammaS binding was verified by coincubating membranes with endomorphins in the presence of specific mu-, delta- or kappa-opioid receptor antagonists. Coincubation with selective mu-opioid receptor antagonists beta-funaltrexamine or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2) (CTOP) blocked both endomorphin-1 and-2-stimulated [(35)S]GTPgammaS binding. In contrast, neither delta- nor kappa-opioid receptor antagonist had any effect on the [(35)S]GTPgammaS binding stimulated by either endomorphin-1 or -2. These findings indicate that both endomorphin-1 and -2 increase [(35)S]GTPgammaS binding by selectively stimulating mu-opioid receptors with intrinsic activity less than that of DAMGO and suggest that these new endogenous ligands might be partial agonists for mu-opioid receptors in the mouse PAG.

Analgesics, Opioid↗
PubMedDate not supplied

c-fos expression as a marker of central cardiovascular neurons.

Immunohistochemical detection of Fos, the protein product of the immediate-early gene c-fos, was evaluated as a functional marker of central neurons sensitive to a change of blood pressure/blood volume. Controlled hemorrhage and infusion of the hypotensive agent nitroprusside or hydralazine induced the appearance of Fos-immunoreactivity (Fos-IR) in several prominent groups of central neurons: the piriform cortex, bed nucleus of the stria terminalis, islands of Calleja, subfornical organ, central nucleus of the amygdala, parabrachial nucleus, supraoptic and paraventricular nuclei, pontine A5, locus ceruleus, ventrolateral medulla, the nucleus of the solitary tract, area postrema, and intermediolateral cell column in the spinal cord. Elevation of blood pressure by infusion of phenylephrine caused the appearance of Fos-IR in fewer groups of neurons: the bed nucleus of the stria terminalis, central nucleus of the amygdala, parabrachial nucleus, the nucleus of the solitary tract and area postrema. The differential distribution of Fos neurons in hypotensive versus hypertensive animals underscores the potential application of Fos as a metabolic marker in identifying a network of neurons responding to a specific cardiovascular challenge. Further, simultaneous characterization of the transmitter phenotype of Fos-containing neurons offers an additional advantage of this method over other conventional tract-tracing techniques.

Animals↗