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D J Reis

Publications and source records attributed to D J Reis.

At least 181 records · Page 10Linked to original sources
PubMed1990

Effect of clonidine on second messenger systems in rat adrenal gland.

Clonidine, an alpha 2-adrenergic agonist, also binds to non-adrenergic imidazole receptors in brain and peripheral tissues. In adrenal medulla, however, clonidine appears to bind only to imidazole receptors. To assess whether the signal transduction mechanism of imidazole receptors differs from alpha 2-adrenergic receptors, we studied the actions of clonidine on the turnover of phosphoinositide and the production of cAMP and cGMP in slices of rat adrenal gland. Clonidine did not modify basal or carbachol mediated increases in phosphoinositide turnover or production of cAMP, however it increased the production of cGMP. The increase in cGMP was slow and unaffected by the addition of the phosphodiesterase inhibitor, IBMX. We conclude that the second messenger response triggered by clonidine in adrenal differs from that usually coupled to alpha 2-adrenergic receptors. Whether the effect is mediated by cell surface imidazole receptors remains to be established.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Maintenance of local cerebral blood flow after acute neuronal death: possible role of non-neuronal cells.

In brain, a major factor regulating local perfusion is local neuronal activity. However, we have recently discovered that, in rat, five days after selective neuronal destruction in the parietal cortex by local microinjections of the excitotoxin ibotenic acid, local cerebral blood flow, within the lesion, remains in the normal range. We studied whether proliferating non-neuronal cells and/or local changes in microvascular density participate to maintain local cerebral blood flow. Rats were anesthetized (halothane 1-3%), ibotenic acid (10 micrograms in 1 microliter) was locally microinjected in a restricted region of the parietal cortex, and animals were allowed to recover. Three, five, seven, 11, 30 days later local cerebral blood flow was measured autoradiographically under chloralose anesthesia (40 mg/kg, s.c.) by the [14C]iodoantipyrine technique. Cellular density or microvascular area were determined on sections stained with Thionine or processed for the endothelial marker alkaline phosphatase, respectively. Local neurons were destroyed by 24 h after microinjections of ibotenic acid. However, from three to 11 days after lesion local cerebral blood flow was unchanged (P greater than 0.05; n = 5), thereafter declining so that by 30 days blood flow was 48 +/- 6% of control (P less than 0.05; n = 5). Cellular density increased within the lesion by 17.5-fold at seven to 11 days (P less than 0.01) and declined to a 11.7-fold elevation above control at day 30 (P less than 0.01). New cells consisted of macrophages, endothelium and glial fibrillary acidic protein-positive astrocytes. The microvascular area increased 4.2-fold from three to 11 days (P less than 0.01). The patency of the presumably newly formed vessels was determined by the presence of intravascular red blood cells, which were revealed histochemically. The area occupied by red blood cells within cerebral microvessels, in contrast to microvascular area, did not increase until seven days after lesion, reaching a 3.2-fold increase at 11 days. Thus within the lesion, local cerebral blood flow remains constant during the phase in which cellular and microvascular density increases. The presumably newly formed vessels cannot contribute to maintain local cerebral blood flow since during this phase they are not patent; rather patency develops coincident with the decline in local cerebral blood flow. We conclude that non-neuronal cells, most likely activated macrophages, may be an important factor regulating local cerebral perfusion, after acute neuronal death.

Alkaline Phosphatase↗
PubMed1990

Continuous monitoring of cerebrocortical blood flow during stimulation of the cerebellar fastigial nucleus: a study by laser-Doppler flowmetry.

Laser-Doppler flowmetry was used to continuously monitor cortical CBF during electrical stimulation of the fastigial nucleus (FN). Rats were anesthetized with isoflurane (0.75-5%), paralyzed, and artificially ventilated. The LDF probe was placed over a target region of the parietal cortex through a burr hole. The hypertension associated with FN stimulation was prevented by spinal cord transection at C1 with arterial pressure maintained by i.v. infusion of phenylephrine. After cord transection, CBF changed linearly with changes in arterial pco2 (r = 0.93; n = 23). FN stimulation (50-100 microA, 50 Hz, 1 s on/1 s off) produced sustained increases in CBF that developed slowly, reaching 50% of maximum within 24 +/- 1 s of stimulation (n = 17). After stimulation, CBF returned to baseline gradually within a time period (84-540 s) proportional to the duration of the stimulation (r = 0.93; n = 15). The CBF response was stimulus frequency and intensity dependent, was elicited only from restricted sites in FN, and was abolished by atropine (1 mg/kg, i.v.) or pentobarbital (30 mg/kg, i.v.). The slow temporal profile of the cerebrovasodilation is compatible with the hypothesis that in cerebral cortex local neurons mediate the vasodilation by interstitial release of vasoactive agents rather than by a direct action of neural processes on blood vessels. LDF is an effective technique for monitoring phasic change in CBF and may be useful in studies of the intrinsic neurogenic control of the cerebral circulation.

Animals↗
PubMed1990

Dissociation by chloralose of the cardiovascular and cerebrovascular responses evoked from the cerebellar fastigial nucleus.

We studied the effects of chloralose anesthesia on the elevation in arterial pressure (AP), heart rate (HR), and regional CBF (rCBF) elicited by stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized with an initial dose of chloralose (40 mg/kg s.c.), paralyzed, and artificially ventilated. The FN was stimulated (50-100 microA, 50 Hz, 1 s on/1 s off) with microelectrodes stereotaxically implanted. During the stimulation AP was carefully maintained within cerebrovascular autoregulation. CBF was measured by the [14C]iodoantipyrine technique with regional dissection. In rats that received only the initial dose of chloralose, FN stimulation elevated rCBF in brain and spinal cord, up to 209 +/- 13% of control in frontal cortex (n = 5; p less than 0.01, analysis of variance). Administration of additional chloralose (10 mg/kg i.v., 30 min prior to measurement of CBF) did not affect resting rCBF (n = 5), the EEG, or the elevation in AP and HR elicited by FN stimulation (n = 4). However, the additional chloralose abolished the elevations in rCBF (n = 5; p greater than 0.05). Thus, the cerebrovasodilation elicited from the FN is more susceptible to the effects of additional anesthesia than the elevation in AP and HR. These results indicate that the cerebrovascular and cardiovascular responses elicited from the FN are functionally distinct and provide additional evidence for the notion that these responses are mediated by different neural pathways and transmitters.

Animals↗
PubMed1990

Characterization and visualization of clonidine-sensitive imidazole sites in rat kidney which recognize clonidine-displacing substance.

In the ventrolateral medulla oblongata, clonidine binds not only to alpha 2-adrenergic receptors but also to a novel class of nonadrenergic sites that are specific for imidazoles. Since clonidine has direct actions on the kidney, we sought to determine whether imidazole binding sites could be detected in renal cell membranes. Adrenergic agents having an imidazole ring, like clonidine, completely displaced the specific binding of the high-affinity clonidine analog 3H-p-aminoclonidine (3H-PAC) to kidney membranes. Nonimidazole adrenergic agents inhibited 3H-PAC binding by only 75%, indicating that the remaining 25% of the sites were nonadrenergic. Cimetidine, an imidazole compound lacking adrenergic potency, showed a high affinity for approximately 25% of the sites. 3H-PAC binding to imidazole sites was high-affinity (KD = 11 +/- 3 nmol/L) and saturable (Bmax = 41 +/- 10 fmol/mg protein). Like clonidine, an endogenous clonidine-displacing substance (CDS) completely inhibited 3H-PAC binding to renal cortex membranes. Quantitative receptor autoradiography revealed that imidazole receptors exhibited a specific regional distribution within the kidney that was unique, and distinct from that of alpha 2-adrenergic receptors. We conclude that clonidine binds to specific imidazole sites in the renal cortex of the rat and that CDS may be the endogenous ligand at these sites. Thus, in addition to their role in central nervous system control of arterial pressure, imidazole receptors may be involved in the regulation of renal function.

Animals↗
PubMed1990

Neuropeptide Y receptor subtypes, Y1 and Y2.

Heterogeneity among NPY (and PYY) receptors was first proposed on the basis of studies on sympathetic neuroeffector junctions, where NPY (and PYY) can exert three types of action: 1) a direct (e.g., vasoconstrictor) response; 2) a postjunctional potentiating effect on NE-evoked vasoconstriction; and 3) a prejunctional suppression of stimulated NE release; the two latter phenomena are probably reciprocal, since NE affect NPY mechanisms similarly. It was found that amidated C-terminal NPY (or PYY) fragments, e.g., NPY 13-36, could stimulate selectively prejunctional NPY/PYY receptors, which were termed Y2-receptors. Consequently, the postjunctional receptors which were activated poorly by NPY/PYY fragments, were termed Y1-receptors. Later work has indicated that the Y2-receptor may occur postjunctionally in selected sympathetic effector systems. The central nervous system appears to contain a mixture of Y1- and Y2-receptors as indicated by functional as well as binding studies. For instance, NPY and NPY 13-36 produced diametrically opposite effects on behavioral activity, indicating the action of the parent peptide on two distinct receptors. Cell lines, most importantly neuroblastomas, with exclusive populations of Y1- or Y2-receptors, have been characterized by binding and second messenger studies. In this work, selective agonists for the two receptor subtypes were used. Work of many investigators has formed the basis for subclassifying NPY/PYY effects being mediated by either Y1- or Y2-receptors. A preliminary subclassification based on effects of NPY, PYY, fragments and/or analogs is provided in Table 6. It is, however, to be expected that further receptor heterogeneity will be revealed in the future. It is argued that mast cells possess atypical NPY/PYY receptors. The histamine release associated with stimulation of the latter receptors may, at least in part, underlie the capacity of NPY as well as of short C-terminal fragments to reduce blood pressure. Fragments, such as NPY 22-36, appear to be relatively selective vasodepressor agents because of their weak vasopressor properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium↗
PubMed1990

Role of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medulla.

The rostral ventrolateral medulla is the primary site of action for clonidine, a centrally acting antihypertensive. In the rostral ventrolateral medulla, clonidine binds not only to alpha-2 adrenergic receptors but also to specific imidazole sites. In order to determine whether a putative imidazole receptor mediates the hypotensive action of clonidine, a series of compounds was tested 1) in vitro for binding affinity at imidazole and alpha-2 sites and 2) in vivo for ability to lower arterial pressure and heart rate when microinjected directly into the rostral ventrolateral medulla. Hypotensive potency was correlated with affinity at imidazole sites (r = 0.84), but not with alpha-2 affinity (r = -0.05). The bradycardia elicited by this series of compounds also correlated with affinity at imidazole receptors (r = 0.89), but not with alpha-2 affinity (r = 0.10). Furthermore, the imidazole idazoxan selectively reversed the fall in arterial pressure elicited by clonidine, whereas SKF-86466, an alpha-2 antagonist which is not an imidazole, failed to attenuate clonidine's action. An imidazole receptor in the rostral ventrolateral medulla appears to mediate the central hypotensive actions of clonidine and related centrally acting imidazoles and may participate in the regulation of arterial pressure and heart rate.

Animals↗
PubMed1990

Magnetic resonance imaging demonstrates that electric stimulation of cerebellar fastigial nucleus reduces cerebral infarction in rats.

We sought to determine whether high spatial resolution magnetic resonance imaging is useful for noninvasive quantitation of the ischemic infarct produced by occlusion of the middle cerebral artery and for detection of reduced infarct volume elicited by electric stimulation of the cerebellar fastigial nucleus. Male rats of the spontaneously hypertensive strain were anesthetized, the middle cerebral artery was occluded, and the fastigial nucleus was stimulated for 1 hour. Twenty-four hours later, rats were reanesthetized and T1- and T2-weighted images were obtained. Rats were killed and the volume and distribution of the lesion was established by histopathology. Magnetic resonance imaging estimates of the lesion volume were 271 +/- 41.0 mm3 (middle cerebral artery, n = 5) and 148 +/- 8.4 mm3 (middle cerebral artery + fastigial nucleus stimulation, n = 6; 45% reduction, p less than 0.05). Histopathological analysis revealed a lesion of 229.8 +/- 15.4 mm3 involving somatosensory cortex, lateral caudate putamen, and lateral hippocampus. Fastigial nucleus stimulation resulted in a 36% reduction in infarct volume to 146.0 +/- 10.3 mm3. The retrieved zone was largely in the cortex dorsal and ventral to the lesion and mostly posterior to the lesion. The estimates of lesion volume by magnetic resonance imaging and histopathology did not differ and were highly correlated (r = 0.90; p less than 0.001). This study confirms our previous finding that fastigial nucleus stimulation reduces the volume of a focal ischemic infarct and demonstrates that magnetic resonance imaging not only accurately estimates the volume of the lesion but also can detect changes as small as 50-100 mm3.

Animals↗
PubMed1990

Identification of a functional glucocorticoid response element in the phenylethanolamine N-methyltransferase promoter using fusion genes introduced into chromaffin cells in primary culture.

The rat gene encoding phenylethanolamine N-methyltransferase (PNMT) was cloned and a consensus sequence for a glucocorticoid response element (GRE) was found at -513 bp, 5' to the transcriptional start site. In order to define the function of this element, fusion genes containing the PNMT promoter and a chloramphenicol acetyltransferase (CAT) reporter gene were constructed. These constructs did not express after transfection into any of 7 continuous cell lines, none of which endogenously produce PNMT. A system for transfecting chromaffin cells in primary culture was therefore devised using constructs containing 200 bp of the proenkephalin (ENK) promoter, whose expression characteristics are well known. pENK beta GAL-1, containing the ENK promoter with a lac Z reporter, was introduced into these cells and beta-galactosidase activity was visualized in situ. Approximately 90% of cells transfected were chromaffin; transfection efficiency was 5%. High levels of CAT activity were measured in chromaffin cells transfected with pENKAT12, possessing a CAT reporter. In contrast to tumor cell lines, pENKAT12 induction in these cells by forskolin and phorbol esters did not require a phosphodiesterase inhibitor. In this chromaffin system, both basal and regulated expression of the PNMT fusion genes were detected. Dexamethasone (dex) induced expression of pPNMT3000 and pPNMT900, containing the putative GRE and 3000 bp or 863 bp of PNMT promoter sequence, 4- to 10-fold. Expression of pPNMT300 and pPNMT100, which lack the GRE and contain 273 bp or 99 bp of PNMT promoter sequence, was unaffected by dex. Addition of the PNMT region spanning -490 to -863 bp conferred full dex responsiveness to a thymidine kinase promoter. Deletion of the putative GRE sequence by site-directed mutagenesis abolished the dex response. These data identify the sequence at -513 bp in the rat PNMT gene as a functional, positively acting GRE. Primary cultures of bovine chromaffin cells provide a biologically relevant expression system for transcriptional studies of catecholamine genes and their related neuropeptides.

Animals↗
PubMed1989

Neuroblastoma-glioma hybrid cells contain clonidine-displacing substance.

Clonidine-displacing substance (CDS) isolated from bovine brain potently inhibits clonidine binding and elicits contraction of gastric smooth muscle. We sought to determine if CDS was contained in neuron-like clonal cells (neuroblastoma X glioma hybrid NG108-15). Extracts were prepared from osmotically shocked P2 fractions of NG108-15 cells. One unit of CDS, as defined by a [3H]p-aminoclonidine radioreceptor assay using bovine frontal cortex membranes, was obtained from each 1.3 million cells processed. CDS isolated from NG108-15 cells was biologically active on gastric smooth muscle. NG108-15 cells may serve as a model system for the study of this endogenous clonidine-like ligand.

Animals↗
PubMed1989

Glutamate in the spinal sympathetic intermediolateral nucleus: localization by light and electron microscopy.

Glutamate immunoreactivity was examined in the sympathetic intermediolateral nucleus (IML) of the thoracic spinal cord using an antibody (Hepler et al., J. Histochem. Cytochem., 36 (1988) 13-22) to hemocyanin-conjugated L-glutamate and the peroxidase-antiperoxidase (PAP) technique. Glutamate labeling was seen in punctate varicosities throughout the IML, in IML neurons and their dendritic processes extending into the lateral funiculus, and diffusely in the IML neuropil. Glutamate labeling was unaffected by preabsorption of the antibody with a conjugate of L-aspartate (100 micrograms/ml) to bovine serum albumin (BSA), but was abolished by similar treatment with a conjugate of L-glutamate (1.7 microgram/ml) to BSA. Glutamate immunoreactivity in the IML was eliminated caudal to T3 spinal transection, while that in the dorsal horn was preserved. Ultrastructural examination of the IML revealed that glutamate was localized within round clear vesicles in axon terminals ranging in diameter from 0.6 to 2.5 microns, and containing several mitochondria, but no dense-core vesicles. Glutamate-containing terminals made primarily asymmetric synapses on small dendrites of IML neurons. These synapses were usually enveloped by processes of astrocytic glia which could also contain glutamate immunoreactivity. The findings provide an anatomic substrate for glutamatergic excitation of sympathetic nerve discharge through a descending spinal pathway terminating in the IML. These data support the hypothesis that sympathoexcitation elicited by stimulation of the rostral ventrolateral medulla may be mediated by a direct glutamatergic pathway to the IML.

Adrenergic Fibers↗
PubMed1989

Local and remote microvascular changes in excitotoxin-induced focal brain lesions.

We have examined the changes in the microvascular diameter, number/mm2 (NA) and area (AAi%) which occur after local brain lesions by the excitotoxin ibotenic acid (IBO). Rats (n = 18) were anesthetized with halothane. IBO (10 micrograms in 1 microliters of phosphate buffer) or vehicle was microinjected in a target region of the parietal cortex via glass micropipettes stereotaxically placed and animals were allowed to recover. Four 9, 15 and 30 days later rats were sacrificed and their brains removed, sectioned (thickness: 20 microns) and processed for the microvascular marker alkaline phosphatase. AAi%, NA and diameter were measured in the area of the lesion and in the homotopic contralateral cortical area by computer-assisted image analysis. In the lesion, AAi% increased by 83% at day 4, reached its maximum at day 9 (+227%) and then declined. Vascular diameter and NA also increased. However while diameter peaked at day 9 (+75%), Na reached its maximum at day 15 (+50%), at a time when AAi% was declining. In the contralateral cortex diameter increased at day 9 (+21%) but NA decreased (-35%) resulting in unchanged vascular area. Thus, focal brain lesions by excitotoxins produce substantial local and remote microvascular changes which have different patterns and may be mediated by distinct cellular and molecular mechanisms.

Animals↗
PubMed1989

Ultrastructural localization of choline acetyltransferase in the rat rostral ventrolateral medulla: evidence for major synaptic relations with non-catecholaminergic neurons.

Pharmacological and biochemical studies suggest that interactions between cholinergic and catecholaminergic and catecholaminergic neurons, particularly those of the C1 adrenergic cell group, in the rostral ventrolateral medulla (RVL) may be important in cardiovascular control. Ultrastructural localization of choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine, and its relation to neurons exhibiting immunoreactivity for catecholamine- (tyrosine hydroxylase; TH) or adrenaline (phenylethanolamine-N-methyltransferase; PNMT) -synthesizing enzymes were examined in the RVL using dual immunoautoradiographic and peroxidase anti-peroxidase (PAP) labeling methods. By light microscopy, the ChAT-immunoreactive neurons were located both dorsally (i.e. the nucleus ambiguus) and ventromedially to those labeled with TH or PNMT (TH/PNMT). A few ChAT-labeled processes were dispersed among TH/PNMT-containing neurons with the majority of overlap immediately ventral to the nucleus ambiguus. By electron microscopy, ChAT-immunoreactivity (ChAT-I) was detected in neuronal perikarya, dendrites, axons and axon terminals and in the vascular endothelial cells of certain blood vessels. The ChAT-labeled perikarya in the ventromedial RVL were medium-sized (15-20 microns), elongated, contained abundant cytoplasm and had had slightly indented nuclei. Synaptic junctions on ChAT-immunoreactive perikarya and dendrites were primarily symmetric with 64% (45 out of 70) of the presynaptic terminals unlabeled. The remaining terminals were immunoreactive for ChAT (30%) or TH/PNMT (6%). Terminals with ChAT-I were large (0.8-2.0 microns) and contained numerous small clear vesicles and 1-2 dense core vesicles. Seventy-seven percent (112 out of 145) of the ChAT-labeled terminals formed symmetric synapses with unlabeled perikarya and dendrites, whereas only 8% were with TH/PNMT-labeled perikarya and dendrites, and 15% were with ChAT-immunoreactive perikarya and dendrites. We conclude (1) that cholinergic neurons in the RVL principally terminate on and receive input from non-catecholaminergic neurons, and (2) that the reported sympathetic activation following application of cholinergic agents to the RVL may be mediated by cholinergic inhibition of local inhibitory interneurons. The observed synapses between ChAT and TH/PNMT-containing neurons suggests that cholinergic and adrenergic neurons additionally may exert a minor reciprocal control on each other and thus may modulate their response to the more abundant input from afferents containing other transmitters.

Animals↗
PubMed1989

Global reduction in cerebral blood flow and metabolism elicited from intrinsic neurons of fastigial nucleus.

We sought to determine whether the global increase in regional cerebral blood flow (rCBF) produced by electrical stimulation of the rostral cerebellar fastigial nucleus (FN) is a consequence of excitation of intrinsic neurons of the FN or of axons of fibers passing through or projecting into it. Studies were conducted in rats anesthetized with chloralose, paralyzed and ventilated. rCBF was measured with [14C]iodoantipyrine as tracer and regional cerebral glucose utilization (rCGU) by [14C]2-deoxyglucose in homogenates of 11 brain regions. Neuronal perikarya in FN were excited chemically by local microinjection of the glutamate analogue kainic acid (KA) (5 nmol in 100 nl). KA elicited a transient and significant fall of arterial pressure and heart rate, the fastigial depressor response (FDR). Associated was a significant and symmetrical reduction in rCBF, to 44% of control in all regions except medulla. The response was site- and agent-specific and unrelated to the hypotension. KA also significantly and proportionally reduced, to 52% of control, rCGU in the same 10 areas of brain. In all regions the magnitudes of the reductions in rCBF and rCGU elicited by KA were linearly related. Intrinsic neurons of FN were chronically destroyed by local microinjection of the excitotoxin ibotenic acid (IBO) (10 micrograms/microliters in 0.4 microliter). Destruction of intrinsic FN neurons had no effect on resting rCBF nor on the global cerebrovascular vasodilation elicited by electrical stimulation of the FN. We conclude that: (a) excitation of intrinsic neurons of FN elicits a widespread reduction of cerebral metabolism and, secondarily, blood flow; (b) FN neurons do not exert a long-term tonic influence on brain blood flow nor metabolism; (c) the global increase in rCBF elicited by electrical stimulation of the FN is a consequence of excitation of axons projecting into or through the nucleus.

Animals↗
PubMed1989

Ultrastructural localization of phenylethanolamine N-methyltransferase-like immunoreactivity in the rat locus coeruleus.

Adrenergic afferents from the rostral ventrolateral medulla are known to modulate the activity of noradrenergic neurons of the locus coeruleus (LC). The light and electron microscopic localization of a polyclonal antiserum directed against the adrenaline synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT) was used to determine the identity and targets of the adrenergic afferents to the LC of the rat brain. By light microscopy, varicose processes showing intense PNMT-like immunoreactivity (LI) were seen throughout the neuropil surrounding neuronal perikarya which in adjacent sections were shown to contain immunoreactivity for the noradrenaline synthesizing enzyme, dopamine-beta-hydroxylase. Electron microscopy confirmed that these labeled varicose processes were primarily axon terminals. Terminals containing PNMT-LI constituted 30% (141 out of 464) of all identifiable terminals within the LC. These terminals were 0.5-1.8 micron in diameter and contained many small, clear and from 2 to 10 larger dense-core vesicles. The targets of the terminals with PNMT-LI were principally unlabeled (i.e. non-PNMT-containing) perikarya and dendrites. The synaptic junctions on perikarya were rare and exclusively symmetric; whereas, those on proximal (large) dendrites were somewhat more numerous and included symmetric as well as asymmetric membrane specializations. However, the vast majority (85% from a total of 141) of the terminals with PNMT-LI formed asymmetric synaptic junctions on unlabeled distal (small) dendrites and dendritic spines. In rare instances, the PNMT-immunoreactive terminals also formed synaptic junctions with other similarly labeled terminals. These findings provide the first ultrastructural evidence that adrenergic terminals in the LC (1) are one of the more prevalent synaptic inputs to the principally noradrenergic neurons; (2) have both symmetric and asymmetric synaptic specializations conventionally associated with inhibition and excitation, respectively; and (3) may modulate other adrenergic terminals through presynaptic mechanisms. In addition to the varicose processes, light microscopy revealed diffuse PNMT-LI throughout the LC. The ultrastructural correlate of this labeling was seen as patches of peroxidase product within the cytoplasm of a few perikarya and dendrites and throughout the cytoplasm of astrocytes identified by their discrete bundles of microfilaments. The detection of PNMT-LI in cells that are not known to synthesize adrenaline is surprising and suggests either a functional diversity for PNMT or amino acid sequence homologies with related enzymes which are enriched in the LC.

Animals↗
PubMed1989

The C1 area of rostral ventrolateral medulla: a central site integrating autonomic responses to hemorrhage.

Activation of the sympathetic neurons and release of adrenomedullary catecholamines are the principal early reflex responses to hemorrhage. These are initiated by arterial baro- and chemoreceptors, from other cardiopulmonary receptors, and by intracerebral receptors responding to ischemia. A principal gateway for integrating the autonomic responses are a small collection of neurons in a region of the rostral ventrolateral medulla (RVL), containing a cluster of neurons of the C1 adrenergic cell group, the C1 area. Neurons in the C1 area of RVL project exclusively to autonomic nuclei of the spinal cord, are tonically active, and fire with a rhythm linked to the cardiac cycle. They are essential for maintaining resting discharge of sympathetic nerves and, consequently, arterial pressure (AP) and heart rate. They also are critical for reflex changes in AP in the baro- and chemoreceptor, somato-sympathetic (pain), and cerebral ischemic reflexes. Neurons of the C1 area are under tonic excitatory and inhibitory control by pathways from other autonomic centers. They are controlled by a range of neurotransmitters including, gamma aminobutyric acid (GABA), acetylcholine, catecholamines, enkephalin, and several neuropeptides. They also serve as a site of action for the hypotensive actions of several clinically important neurotransmitters. The C1-area of RVL may play a critical role in the autonomic responses to hemorrhage and may be an important target for drugs seeking to treat hemorrhagic shock.

Animals↗
PubMed1989

Adrenergic neurons in the rostral ventrolateral medulla: ultrastructure and synaptic relations with other transmitter-identified neurons.

The first part of this chapter demonstrates that the C1 adrenergic neurons have high mitochondrial content and a close proximity to capillaries and glia suggestive of a high metabolic activity and a possible chemosensory function. Adrenergic terminals arising primarily from these neurons (1) can influence sympathetic nerve discharge through direct contacts on sympathetic preganglionic neurons in the IML of the spinal cord; and (2) are one of the more prevalent synaptic inputs to the principally noradrenergic neurons in the locus coeruleus. In both the IML and locus coeruleus, adrenergic terminals may be either excitatory (asymmetric synapses) or inhibitory (symmetric synapses) depending on their distribution on the post-synaptic target. The second part of this chapter shows that C1 adrenergic neurons in the RVL are modulated by synaptic associations with a variety of transmitter systems (see schematic Fig. 8). Specifically, C1 adrenergic neurons receive (1) major inhibitory input (symmetric synapses) from GABA-ergic and opioid terminals as well as from unidentified (unlabelled) transmitter-containing terminals; (2) major excitatory input (asymmetric synapses) from terminals containing substance P as well as other unidentified terminals and (3) minor inputs from cholinergic, adrenergic and noradrenergic pathways. Moreover, cholinergic terminals in the RVL form symmetric synapses mainly on unidentified transmitter-containing neurons rather than the C1 neurons suggesting that the reported cardiovascular effects of cholinergic agents in the RVL are most likely mediated via inhibitory interneurons. Within the RVL, adrenergic and noradrenergic terminals innervate cholinergic and opioid neurons. Thus, these results not only provide direct evidence that a number of transmitters modulate the activity of C1 adrenergic neurons, but also suggest new directions for studies of functional interactions involving catecholaminergic regulation of other transmitter-containing neurons within the RVL.

Animals↗