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J J Dreifuss

Publications and source records attributed to J J Dreifuss.

At least 19 recordsLinked to original sources
PubMed1998

Vasopressin and oxytocin action in the brain: cellular neurophysiological studies.

During the last two decades it has become apparent that vasopressin (VP) and oxytocin (OT), in addition to playing a role as peptide hormones, also act as neurotransmitters. Morphological studies and electrophysiological recordings have shown a close anatomical correlation between the presence of these receptors and the neuronal responsiveness to VP or OT. These compounds have been found to affect membrane excitability in neurons located in the hippocampus, hypothalamus, lateral septum, brainstem, spinal cord and superior cervical ganglion. Sharp electrode intracellular and whole-cell recordings, done in brainstem motoneurons, have revealed that VP and OT can directly affect neuronal excitability by opening non-specific cationic channels. These neuropeptides can also influence synaptic transmission, by acting either postsynaptically or upon presynaptic target neurons or axon terminals. Whereas in some hypothalamic neurons OT appears to mobilize intracellular calcium, as revealed by calcium imaging techniques, in the brainstem the action of this neuropeptide is mediated by a second messenger which is distinct from the second messenger activated in peripheral target cells. Future studies should be aimed at elucidating the properties of the cationic channels responsible for the neuronal action of VP and OT, at identifying the brain-specific second messengers activated by these neuropeptides and at determining whether endogenous VP and OT can exert neuronal effects similar to those elicited by exogenous neuropeptides.

Brain Chemistry↗
PubMed1997

Properties of a new radioiodinated antagonist for human vasopressin V2 and V1a receptors.

A vasopressin receptor antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid), 2-o-ethyl-D-tyrosine, 4-valine, 9-tyrosylamide] arginine vasopressin (d(CH2)5[o-ethyl-D-Tyr2,Val4,Tyr-NH9(2)]AVP), has been prepared. This antagonist is a potent antiantidiuretic, antivasopressor and antioxytocic peptide with pA2 values of 7.69-7.94 and affinities of 1.12-11.0 nM. When radioiodinated at the phenyl moiety of the tyrosylamide residue at position 9, this peptide was demonstrated to bind to vasopressin V2 and V1a receptors with a dissociation constant of 0.22-0.75 nM. This ligand is a good tool for further studies on human vasopressin V2 receptor localization and characterization, when used in combination with a selective vasopressin V1a ligand.

Animals↗
PubMed1997

Whole-cell NMDA-evoked current in suprachiasmatic neurones of the rat: modulation by extracellular calcium ions.

The action of N-methyl-D-aspartic acid (NMDA) on suprachiasmatic neurones was studied using whole-cell recordings in coronal hypothalamic slices of the rat. The location of the recorded neurones within the suprachiasmatic nucleus was ascertained by intracellular labelling with biocytin, followed by histological processing of the slice. Suprachiasmatic neurones had an input resistance of 780 +/- 20 M omega (mean +/- S.E.M.; n = 106). They were voltage-clamped at or near their resting membrane potential and their responsiveness to NMDA was tested by adding this compound to the perfusion solution. NMDA generated an inward current in about 85% of the neurones. At 50 microM, the average induced peak current was 30 +/- 10 pA (n = 32); at 100 microM, it was 50 +/- 10 pA (n = 12). The NMDA-induced current was reduced by D-2-amino-5-phosphopentanoic acid (D-AP5), and NMDA receptor antagonist, and was suppressed by MK-801, and NMDA channel blocker. Reducing the extracellular magnesium concentration from 1 to 0.01 mM caused a 2- to 3-fold increase in the amplitude of this current. Thus, suprachiasmatic neurones are endowed with functional NMDA receptor-channels, which may play a role in glutaminergic transmission in this nucleus. Decreasing the extracellular calcium concentration from 2 to 0.01 mM caused a 1.3- to 4.5-fold enhancement in the whole-cell NMDA current. This effect was probably not mediated by a change in the intracellular free calcium concentration. Indeed, loading suprachiasmatic neurones with 11 or 20 mM of the calcium chelator, 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetracetic acid (BAPTA) suppressed a calcium-dependent slowly decaying outward aftercurrent but did not affect the low-calcium-induced facilitation of the NMDA response. NMDA current-voltage relations were established in normal and low-calcium perfusion solutions. In the normal solution, the net current generated by NMDA contained a region of negative slope conductance and reversed in polarity at 7 +/- 2 mV. In the low-calcium solution, this current increased in amplitude in the region of negative slope conductance, whereas at more depolarized potentials it was not altered. The NMDA-induced current was fitted using the Boltzmann equation. The effect of a low-calcium solution could be modelled by shifting the activation of the NMDA-sensitive conductance in the negative direction, by about 17 mV. We conjecture that lowering external calcium can unmask negative surface charges located on or near the NMDA channel and that this, in turn, weakens the voltage-dependent block of the channel by magnesium. A voltage-dependent blockade of the NMDA channel by calcium, however, may be also contribute to this effect. This low-calcium-induced facilitation of the NMDA response could play a regulatory role by enhancing calcium influx through the NMDA channel in case of calcium depletion in its vicinity.

Animals↗
PubMed1997

The oxytocin-induced inward current in vagal neurons of the rat is mediated by G protein activation but not by an increase in the intracellular calcium concentration.

The neuropeptide oxytocin can depolarize parasympathetic preganglionic neurons in the dorsal motor nucleus of the vagus nerve of the rat by generating a sustained inward current, which is sodium-dependent and tetrodotoxin-insensitive. The second messenger activated by oxytocin receptor binding is, however, not yet known. In the present study, we attempted to characterize it by using the whole-cell recording technique and brainstem slices. When loaded with GTP-gamma-S, a non-hydrolysable analogue of GTP, vagal neurons generated a persistent inward current in the absence of agonist and the oxytocin effect was suppressed, suggesting that the peptide-evoked current was mediated by G-protein activation. Loading vagal neurons with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid (BAPTA) suppressed a calcium-dependent, slowly decaying potassium aftercurrent but did not affect the oxytocin response, suggesting that the latter was not mediated by an agonist-induced increase in the intracellular calcium concentration. Protein kinase C (PKC) activation was probably not involved, since the peptide-evoked current was not modified by loading neurons with the PKC inhibitor H7. Thus, the oxytocin-evoked current in vagal neurons was probably not mediated by phospholipase C-beta (PLC-beta) activation. Loading neurons with 8-Br-cAMP or with an adenylyl cyclase activator (forskolin) reduced the oxytocin-evoked current by about half. SQ 22536, an adenylyl cyclase inhibitor, reduced this current by a similar amount. However, the peptide-evoked current was unaffected by Rp-cAMPS and Sp-cAMPS, an inhibitor and an activator, respectively, of cAMP-dependent protein kinase (PKA). We suggest that oxytocin activates two distinct signalling pathways in vagal neurons: one which is cAMP-dependent, but PKA-independent, and one, unidentified, which is PLC-beta-and cAMP-independent. Each pathway accounts for about half of the peptide effect and both appear to involve G-protein activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Vasopressin binding in the cerebral cortex of the Mongolian gerbil is reduced by transient cerebral ischemia.

In Mongolian gerbils, the content of vasopressin in the cerebral cortex, the striatum, and the hypothalamus is increased after induction of acute cerebral ischemia. We used an iodinated vasopressin analogue and light microscopic autoradiography to study the distribution of vasopressin V1 receptors in the brain of adult male gerbils and to evaluate the effects of a transient bilateral cerebral ischemia (6 minutes) on the density of this receptor population. The animals were killed immediately or 10, 30, or 100 hours after transient bilateral occlusion of the common carotid arteries. In control animals, specific [125I]-VPA binding sites were present in various structures of the brain (olfactory bulb, anterior olfactory nucleus, lateral septum, bed nucleus of the stria terminalis, median preoptic area, ventral pallidum, substantia innominata, amygdala, thalamus, hypothalamic mammillary nuclei, superior colliculus, subiculum, central gray, nucleus of the solitary tract, hypoglossal nucleus). The strongest labeling was detected in the cerebral cortex, layers 5-6. After 30-100 hours of survival time following ischemia there was a marked decrease in [125I]-VPA binding site density in these cerebral cortex layers. To a lesser degree, a decrease was also detected in the lateral septal nucleus. In contrast, labeling in other noncortical structures remained unchanged. All animals with 100 hours recovery showed a loss of cells in hippocampus (CA1 layer) and striatum. In addition, ischemia induced concomitant and proliferative changes in cortical and hippocampal astrocytes assessed by glial fibrillary acid protein immunoreactivity. These observations indicate a role for vasopressin in the cerebral cortex either on neurons or on glial cells and the modulation of vasopressin receptor expression by transient cerebral ischemia.

Animals↗
PubMed1995

Reduced binding of oxytocin in the rat brain during aging.

Central oxytocin (OT) receptors were labelled in 3-month-old and 20-month-old rats with an iodinated OT antagonist. Comparison of the autoradiograms by quantitative image analysis revealed in the old animals a significant reduction of binding in three regions; the number of labelled OT receptors was decreased by 90% in the head of the caudate putamen, by 68% in the olfactory tubercle, and by 41% in the ventromedial hypothalamic nucleus. Previous studies had shown that the expression of OT receptors in the olfactory tubercle and in the ventromedial hypothalamic nucleus was dependent upon gonadal steroids. Therefore we hypothesize that the reduced number of OT receptors in the latter two structures of aged rats was the consequence of the 4-fold decrease of plasma testosterone that we found in this age. Another mechanism may be responsible for the marked reduction of OT receptors in the caudate putamen.

Aging↗
PubMed1995

Characterization of a novel, linear radioiodinated vasopressin antagonist: an excellent radioligand for vasopressin V1a receptors.

We report on the pharmacological properties of a potent and selective linear vasopressin (AVP) V1a receptor antagonist HO-Phenylacetyl1-D-Tyr(Me)2-Phe3-Gln4-Asn5-Arg6-Pro7-Arg8-NH2 (HO-LVA). Iodinated on the phenolic substituent at position 1, [125I]-HO-LVA displayed the highest affinity for rat liver V1a receptors (8 pM) ever reported. Furthermore, affinities of HO-LVA and I-HO-LVA for V1b, V2 and oxytocin (OT) receptors was 400- to 1,000-fold lower than for V1a receptors, rendering it a highly selective ligand. Both HO-LVA and its iodinated derivative are V1 antagonists, they potently inhibited AVP-induced inositol-phosphate accumulation in WRK1 cells, and also, although with a much lower potency, the AVP-induced ACTH release from freshly prepared pituitary cells. Using autoradiography [125I]-HO-LVA appeared to be the first radioligand to successfully identify and localize the presence of V1a receptors in rat liver and blood vessel walls. Moreover, several new brain regions expressing V1a receptors could be identified, in addition to those brain regions that were previously identified with other radiolabelled AVP analogues.

Adrenocorticotropic Hormone↗
PubMed1994

Axotomy induces the expression of vasopressin receptors in cranial and spinal motor nuclei in the adult rat.

8-L-Arginine vasopressin ([Arg8]VP) receptors are expressed transiently in the rat facial nucleus during the perinatal period. Electrophysiological studies suggest that at least part of these receptors is located on facial motoneurones. In the present study we report that, in the adult rat, unilateral section of a facial nerve results in a massive and transient reexpression of [Arg8]VP receptors in the deeferented facial nucleus. Data were obtained by quantitative film autoradiography. During the first 2 postoperative weeks, binding of an iodinated ligand selective for V1a-type receptors increased about 10-fold. Maximal levels of binding were maintained for 1-2 weeks and then started to decrease. Binding was not strictly restricted to the facial nucleus but included the neuropile between motoneuronal pools and the perifacial area, which may indicate a dendritic localization of [Arg8]VP receptors. To investigate whether other motor nuclei also react to axotomy by up-regulating [Arg8]VP receptors, we sectioned either a hypoglossal nerve or a sciatic nerve. Two weeks after surgery, the hypoglossal nucleus or sciatic motoneuronal pools ipsilateral to the lesion were intensely labeled with the iodinated ligand. In contrast, nerve section had no effect on oxytocin binding sites in facial, hypoglossal, or sciatic motor nuclei. The results suggest that [Arg8]VP receptor expression in motor nuclei may depend upon neuromuscular contacts and, thus, that [Arg8]VP may be involved in the establishment of neuromuscular connections during development and in their reestablishment after nerve injury.

Amino Acid Sequence↗
PubMed1994

Action of vasopressin on hypoglossal motoneurones of the rat: presynaptic and postsynaptic effects.

The distribution of vasopressin binding sites in the hypoglossal nucleus of newborn rats was determined using autoradiography on film and a radioiodinated vasopressor antagonist. These sites predominated in the ventromedial and dorsal divisions of the nucleus. The effect of vasopressin on hypoglossal neurones was studied in brainstem slices of newborn animals, using the single-electrode voltage-clamp technique. Vasopressin, at 0.1-0.5 microM, generated a sustained inward current in a majority of neurones, an action which was mediated by V1-type receptors. Antidromic activation or morphological characterization of biocytin-labelled neurones indicate that part of the vasopressin-sensitive cells were motoneurones. When synaptic transmission was blocked by perfusing the preparation with a low-calcium/high-magnesium solution, the average vasopressin current decreased by 65%; and following TTX treatment, the peptide current decreased by 55%. In contrast, in a low-calcium solution, i.e., under conditions of reduced synaptic transmission but of increased neuronal excitability, the vasopressin current was not significantly altered. These results may be interpreted by assuming that the action of vasopressin is in part postsynaptic and in part presynaptic, the latter effect probably depending upon action potential propagation. Current-voltage relations suggest that the postsynaptic effect of vasopressin was due to the induction of a non-inactivating inward current, reversing in polarity at around -15 mV. The data raise the possibility that, in young animals, endogenous vasopressin may modulate the activity of hypoglossal motoneurones.

Afferent Pathways↗
PubMed1994

Regional differences in testosterone effects on vasopressin receptors and on vasopressin immunoreactivity in intact and castrated Siberian hamsters.

Vasopressin binding sites were detected in the brain of the Siberian hamster, using [3H]vasopressin and a 125I-labelled linear vasopressin antagonist specific for V1 vasopressin receptors. In the ventromedial and premammillary nuclei, the density of the binding was lower in the females than in the males. The effect of castration and of testosterone replacement was assessed in males. Two distinct effects were observed. Orchidectomy diminished significantly the vasopressin binding in the ventromedial nucleus, an effect which was prevented by implantation of a mini-pump releasing testosterone. On the contrary, in the premammillary nucleus no significant differences were noticed following castration and testosterone treatment. In addition, vasopressin immunoreactivity was examined in males, in females and in castrated males. No sex differences were evident. However, in the bed nucleus of the stria terminalis and the lateral septal nucleus, castration decreased vasopressin immunoreactivity in either sex. This effect of castration was prevented by testosterone. Vasopressin immunoreactivity was detected neither in the ventromedial nor in the premammillary hypothalamic nuclei. Our observations suggest that, in adult Siberian hamster premammillary nucleus, the expression of vasopressin receptors is not controlled by gonadal steroids but is sex related and could be induced during fetal or early postnatal life.

Animals↗
PubMed1994

Vasopressin-binding sites in the pig pituitary gland: competition by novel vasopressin antagonists suggests the existence of an unusual receptor subtype in the anterior lobe.

Arginine vasopressin (AVP) acts in the pituitary gland, in synergy with corticotrophin-releasing factor, to induce ACTH release in response to stressful stimuli. Pituitary AVP receptors in the rat are coupled to phospholipase C, as are the so-called V1-type AVP receptors. The present study examined [3H]AVP binding in membranes prepared from the anterior lobe of the pituitary gland of the pig. [3H]AVP, alone or in competition with analogues, bound to sites in the pig anterior lobe which are pharmacologically similar to those described previously by others in the rat pituitary gland. For comparison, the same competition studies were performed on membrane preparations from the rat liver which contain the classic V1-type AVP receptor. Pituitary and liver AVP-binding sites were dissimilar; both cyclic and linear V1 antagonists had, in general, a much lower affinity for pituitary AVP-binding sites than for those in the liver. Thus, Phaa-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 (Phaa = phenylacetyl) has a 2500-fold greater affinity for the latter (negative logarithm of inhibition constant (pKi) = 9.64) than for the former (pKi = 6.22). One linear antagonist, Pa-D-Tyr-Phe-Val-Asn-Arg-Pro-Arg-Arg-NH2 (Pa = propionyl) had about equal affinities for liver and pituitary membranes (pKi = 6.39 and 6.53 respectively). Another compound, Phaa-D-Tyr-Phe-Val-Asn-Arg-Pro-Arg-Arg-NH2 had the highest affinity found to date for binding to AVP sites in the pituitary (pKi = 7.43). These findings suggest some ideas for the design of more potent and/or selective AVP analogues acting in the pituitary gland.

Amino Acid Sequence↗
PubMed1993

Modulation by divalent cations of the current generated by vasopressin in facial motoneurons.

Vasopressin generates a voltage-gated, sodium-dependent current in facial motoneurons in brainstem slices. Reducing the extracellular calcium concentration from 2 to 0.01 mM caused a 30 to 120% increase in the amplitude of this current. Lowering extracellular magnesium also enhanced it, but less efficiently. In the physiological solution, the response of facial neurons to vasopressin is thus partially blocked. Increasing extracellular calcium was without effect. Current-voltage curves indicate that the vasopressin current reversed at around 0 mV and suggest that the low-calcium-induced potentiation was due to an attenuation of the region of negative slope conductance.

Animals↗
PubMed1993

Mapping of [3H]vasopressin binding sites in the brain of jerboa (Jaculus orientalis) by an high resolution beta-radio imager.

The distribution of vasopressin receptors in the brain of the jerboa (Jaculus orientalis) was studied using tritiated arginin vasopressin ([3H]vasopressin). beta-Particles emitted from tritiated ligand bound to brain sections were detected by a newly developed beta-radio imager to generate a light spot which was read by a charge coupled device camera. The number and coordinate of the center of gravity of the light spot were recorded. After summation in pixels of the counts collected during 2-20 h, an image was produced representing the distribution of [3H]vasopressin bound to brain sections. Specific vasopressin binding was detected in various brain regions such as the cerebral cortex, islands of Calleja, pallidum, amygdala and the hippocampus as well as in the pituitary gland. The intensity of the binding was quantified directly from the images obtained and expressed in decays/min/surface unit. The linearity of this method of detection allowed a relevant measurement of non-specific binding, therefore its subtraction from images representing the total binding. Three-dimensional reconstructions of labeled structures were also performed. The presence of numerous vasopressin receptors in the jerboa hippocampus suggests a major role for this neuropeptide in this part of the brain.

Animals↗