Biomedical subjects

D J Reis

Publications and source records attributed to D J Reis.

At least 163 records · Page 9Linked to original sources

PubMed1991

Effects of clonidine and other imidazole-receptor binding agents on second messenger systems and calcium influx in bovine adrenal chromaffin cells.

Clonidine and related imidazoline compounds bind to alpha 2-adrenergic as well as to newly described non-adrenergic imidazole/imidazoline receptors in brain and peripheral tissues. The present study was undertaken to identify the signal transduction mechanism coupled to this new class of receptors (imidazole receptors) using bovine adrenal chromaffin cells. Clonidine did not modify the basal or forskolin-stimulated production of cyclic AMP (cAMP), suggesting the absence of functionally active alpha 2-adrenergic receptors in adrenal chromaffin cells. Clonidine also failed to modify the basal and GTP gamma S- or carbachol-stimulated increase in phosphoinositide hydrolysis. However, clonidine increased significantly the production of cyclic GMP (cGMP) as well as the uptake of 45Ca2+. The cGMP response to clonidine was slower (peak at 15 min) and smaller (only about 50% over control) than the response to acetylcholine and was not shared by other agents that bind to imidazole receptors. In contrast, all agents that bind to imidazole receptors increased the influx of 45Ca2+ into chromaffin cells. It is concluded that (a) alpha 2-adrenergic and imidazole receptors are functionally distinct and linked to different signal transduction mechanisms; (b) the classical G-protein coupled soluble second messenger systems are not coupled to imidazole receptors; (c) clonidine may increase cGMP by a non-receptor-mediated intracellular action; and (d) imidazole receptors may regulate intracellular calcium levels through an ion regulating system that may be different from calcium channels.

Adrenal Glands↗

PubMed1991

Rostral ventrolateral medulla: a source of the glutamatergic innervation of the sympathetic intermediolateral nucleus.

To determine whether the sympathoexcitatory projection from the rostral ventrolateral medulla (RVL) to the sympathetic intermediolateral nucleus (IML) of the spinal cord might use glutamate as an excitatory transmitter, we performed a dual-label, transport and immunocytochemical ultrastructural study. Axon terminals within the IML were examined to determine whether anterogradely transported Phaseolus vulgaris-leucoagglutinin (PHA-L) following injections into the RVL, was colocalized with glutamate immunoreactivity using an antibody to hemocyanin-conjugated L-glutamate (Hepler et al., J. Histochem. Cytochem., 36 (1988) 13-22). Transported PHA-L was visualized with the peroxidase-antiperoxidase technique while glutamate-like immunoreactivity was localized within the same section of the thoracic spinal cord with immunoautoradiography. By light microscopy, PHA-L immunoreactivity was found within a plexus of fine fibers and varicose processes localized to the IML. Silver grains indicative of glutamate immunoreactivity were concentrated over the IML and also over the superficial layers of the dorsal horn. Electron microscopic analysis revealed PHA-L immunoreactivity in axons and axon terminals within the IML. They ranged in diameter from 0.5 to 2.0 microns, contained numerous small clear and 0-3 large, dense-core vesicles, and formed primarily asymmetric synaptic contacts on small dendrites of IML neurons. Some of the PHA-L immunoreactive terminals making asymmetric (excitatory) synaptic contacts on the small dendrites of IML neurons also contained glutamate-like immunoreactivity. We conclude that at least a portion of the input to the IML from the RVL uses glutamate as its transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Receptor-selective analogs demonstrate NPY/PYY receptor heterogeneity in rat brain.

Neuropeptide Y (NPY) receptors are heterogeneous, consisting of at least two subclasses, Y1 and Y2. We sought evidence for differential expression of NPY receptor subtypes in the rat brain. Tissue was incubated with 125I-peptide YY (PYY) which labels NPY and PYY binding sites. The Y1-selective agonist, p[Pro34]NPY, and the Y2-selective agonist, pNPY 13-36, were used as displacing ligands. Autoradiographic analyses of regional receptor binding demonstrated heterogeneity across brain regions. We conclude that Y1- and Y2-receptors may be independently expressed in the brain. While the predominate NPY/PYY receptor subtype in the brain is Y2, there are also Y1-receptors in some brain regions such as the superficial layers of the parietal cortex.

Animals↗

PubMed1991

Rilmenidine lowers arterial pressure via imidazole receptors in brainstem C1 area.

We sought to determine the site of action and receptor type responsible for the antihypertensive actions of rilmenidine, an oxazoline analogue of clonidine. In anesthetized paralyzed rats decerebration did not alter the dose dependent reductions in arterial pressure and heart rate elicited by i.v. drug. Rilmenidine microinjected bilaterally into the C1 area of the rostral ventrolateral medulla (RVL), but not nucleus tractus solitarii (NTS) nor caudal ventrolateral medulla (CVL), elicited dose-dependent falls in arterial pressure and heart rate at doses an order of magnitude less than required systemically. Prior microinjection into the C1 area of the selective alpha 2-adrenoceptor antagonist SKF-86466, even at high doses, failed to modify the hypotension to i.v. rilmenidine. However, microinjection of 3- to 10-fold lower doses of idazoxan, a ligand for imidazole as well as alpha 2-adrenoceptors, blocked the effects. Rilmenidine also competed with the clonidine analogue [3H]p-aminoclonidine ([3H]PAC) at specific binding sites in membranes of bovine ventrolateral medulla and frontal cortex. In RVL rilmenidine competed with binding to imidazole and alpha 2-adrenergic binding sites with a 30-fold selectivity for the imidazole binding sites. In frontal cortex binding was of lower affinity and restricted to alpha 2-adrenergic sites. We conclude that rilmenidine, like clonidine, acts to lower arterial pressure by an action on imidazole receptors in the C1 area of RVL. The higher selectivity of rilmenidine for imidazole to alpha 2-adrenoceptors as compared to clonidine may explain the lower sedative effects of rilmenidine.

Animals↗

PubMed1991

Cocaine-induced reduction of brain neuropeptide Y synthesis dependent on medial prefrontal cortex.

Repeated administration of cocaine elicits substantial, long-lasting, but reversible reductions in neuropeptide Y (NPY) and NPY mRNA in the rat cerebral cortex and nucleus accumbens. The NPY reduction appears to be mediated through a decrease in NPY biosynthesis, occurring transneuronally, perhaps in response to changes in synaptic dopamine associated with mesolimbic and mesocortical dopamine neurons. The medial prefrontal cortex appears necessary for maintenance of cocaine's action on this neuronal network since excitotoxic lesions of this area prevented (lesion before cocaine) and reversed (lesion after cocaine) the reductions in NPY elicited by the cocaine. NPY may be a sensitive marker for chronic cocaine use. Its decrease may relate to the anxiety and depression associated with cocaine withdrawal in humans.

Animals↗

PubMed1991

Long-lasting inhibition of the cardiovascular responses to glutamate and the baroreceptor reflex elicited by neuropeptide Y injected into the nucleus tractus solitarius of the rat.

Neuropeptide Y (NPY) microinjected unilaterally into the nucleus tractus solitarii (NTS) of anesthetized paralyzed rats elicits a gradual dose-dependent and reversible fall in arterial pressure (AP) and heart rate (HR) lasting 20 min. It also abolished the brief (less than 1 min) dose-dependent and reversible fall of AP and HR elicited by L-glutamate (L-Glu) injected into the nucleus. The blockade of L-Glu by NPY appeared gradually and was prolonged, lasting over 2 h, and recovering by 24 h. It was not replicated by desamido-NPY or galanin. Unlike 2% lidocaine it did not block the hypotension elicited by focal electrical stimulation at the injection site indicating the response was not that of a local anesthetic. Bilateral injection of NPY into the NTS resulted, after an initial fall, in an elevation of AP (+48 +/- 10.6 mmHg). At this time the reflex bradycardia evoked by elevating AP with phenylephrine was markedly reduced. We conclude that in the NTS, NPY antagonizes the actions of L-Glu and may attenuate baroreceptor reflexes. Since the NTS is richly innervated by NPY neurons and contains many NPY binding sites and since primary baroreceptor afferents appear to be glutamatergic the results suggested that NPY may serve in NTS as a long-term regulator of baroreceptor reflex activity.

Animals↗

PubMed1991

Electrical stimulation of cerebellar fastigial nucleus reduces ischemic infarction elicited by middle cerebral artery occlusion in rat.

Electrical stimulation of the cerebellar fastigial nucleus (FN) globally and profoundly increases cerebral blood flow via a cholinergic mechanism. In cerebral cortex, the vasodilation is unassociated with alterations in cerebral glucose utilization, a condition favoring protection against cerebral ischemia. We sought to determine whether FN stimulation would modify the size of the focal ischemic infarction resulting from occlusion of the middle cerebral artery (MCA). The MCA was occluded in anesthetized rats of the spontaneously hypertensive (SHR) or Sprague-Dawley (SD) strains with or without 1 h of electrical stimulation of the FN. Twenty-four hours later, rats were killed and the volume of the infarction established in thionin-stained sections. in SHRs, FN stimulation reduced by 40% the well-established cortical and partially subcortical infarctions elicited by occlusion of the MCA (from 186 +/- 35.2 to 113 +/- 47.1 mm3, mean +/- SD, n = 15; p less than 0.001). The zone of retrieval was anatomically constant, consisting of a rim of cortex dorsal and ventral to the infarction and medially within the thalamus and striatum corresponding to the penumbral zone described by others. The effect was comparable in rats of the SD strain having smaller infarctions. The effect of FN stimulation appears to be selective for the FN system in that it is not evoked by stimulation of the dentate nucleus and is blocked by systemic administration of atropine (1.0 mg/kg). We conclude that excitation of an intrinsic system in brain represented in the rostral FN has the capacity to reduce substantially an ischemic infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Differentiation of two cardiovascular regions within caudal ventrolateral medulla.

The caudal ventrolateral medulla (CVLM) plays a significant role in the regulation of sympathetic nerve activity (SNA) and arterial pressure; however, the use of lesions to examine its role in mediating baroreceptor reflex control of SNA has yielded discrepant results. We hypothesize that this may have arisen from anatomic segregation of neurons within the CVLM that subserve different functions in sympathetic control. Thus we used microinjections of the excitotoxic agent kainic acid (200 pmol in 20 nl) to determine the effects of inactivation of neuronal cell bodies in a rostral and a caudal subregion of the CVLM on SNA, arterial pressure, and baroreceptor reflex function in urethan-anesthetized rats. Interruption of neuronal activity in the rostral CVLM (sites from 0.6 mm caudal to 0.5 mm rostral to the rostral border of the lateral reticular nucleus) elevated SNA (post-kainic acid 214% of control) and arterial pressure (+34 mmHg) and eliminated the inhibition of splanchnic SNA evoked by either aortic nerve stimulation or the pressor response to intravenous norepinephrine. In addition, the cardiac-related component of spontaneous SNA was abolished as judged from post-R wave averages and from power spectral analysis. In contrast, although a similar disruption of neuronal activity in the caudal CVLM (sites 0.0-0.6 mm rostral to the caudal border of the lateral reticular nucleus) produced a comparable increase in spontaneous SNA (post-kainic acid 196% of control) and arterial pressure (+20 mmHg), it was without effect on the ability of the baroreceptor reflex to inhibit SNA, and it enhanced the synchronization of the spontaneous bursts in SNA to the cardiac cycle. Our results suggest an organization of the CVLM in which neurons in its rostral portion are required for an effective baroreceptor reflex, whereas those in the caudal CVLM serve to limit SNA and blood pressure independent of the baroreceptor reflex.

Animals↗

PubMed1991

Responses of sympathetic preganglionic neurons to rostral ventrolateral medullary stimulation.

Sympathoexcitatory pathways from the rostral ventrolateral medulla (RVL) play a significant role in maintaining the tonic discharge of sympathetic preganglionic neurons (SPNs) and, in turn, resting arterial pressure. We examined the responses of antidromically identified, splanchnic SPNs to single stimuli applied to the RVL. Four characteristic response patterns were observed. Forty-five percent (group 1) of responsive SPNs were excited with latencies between 15 and 41 ms (mean 27 ms). The spontaneous activity of these SPNs (mean 3.3 Hz) was strongly modulated by the baroreceptor reflex. Twenty-three percent (group 2) of SPNs were excited with a significantly longer latency (mean 108 ms) and frequently exhibited little spontaneous discharge. Twenty-one percent (group 3) were excited at both short (mean 29 ms) and long (mean 117 ms) latencies. Eleven percent (group 4) of responsive splanchnic SPNs had a biphasic response to RVL stimulation consisting of an early inhibition followed by a late, longer lasting increase in discharge probability. Spontaneous discharge of group 4 SPNs (mean 6.2 Hz) was significantly higher than other groups and was not related to the cardiac cycle (mean arterial pressure 105 mmHg). Microinjection of kainic acid into the RVL greatly reduced the short- and long-latency splanchnic nerve excitations evoked by RVL stimulation. The heterogeneity of the RVL stimulus-evoked responses in splanchnic SPNs may reflect specificity in the descending regulation of functionally distinct subsets of SPNs regulating the various tissues in the splanchnic distribution.

Action Potentials↗

PubMed1991

Neuropeptide Y acts at an atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem.

Microinjection of neuropeptide Y (NPY) into the nucleus tractus solitarius (NTS) induces an initial and reversible fall in arterial pressure (AP) and heart rate (HR), along with a delayed and long-lasting blockade of cardiovascular responses to L-glutamate (L-Glu) injected into the same site and an inhibition of the baroreflex arc. By injecting NPY-receptor subtype selective agonists and NPY-related peptides into NTS we have sought to characterize the receptors that mediate these responses. Unilateral injections into NTS (9-90 pmol) of NPY as well as the Y1 receptor selective agonist [34Pro]NPY and the Y2 receptor selective fragment NPY 13-36 evoked comparable dose-dependent falls of AP and HR in the anesthetized and paralyzed rat. Injections into NTS of peptide YY or pancreatic polypeptide had no effect. Preinjection of NPY, [34Pro]NPY, NPY 13-36 (all at 90 pmol) as well as norepinephrine (6.7 nmol) virtually abolished the fall in AP and HR evoked by subsequent injections of L-Glu into NTS. Injection of peptide YY or pancreatic polypeptide (both at 90 pmol) did not affect the cardiovascular responses evoked by L-Glu in NTS. Injection of NPY (90 pmol) into the caudal ventrolateral medulla induced a slight fall in AP of -17 +/- 5 mm Hg (P less than .05) and a sustained fall in HR of -44 +/- 8 beats per min (P less than .01). Injection of NPY also abolished the fall in HR and AP evoked by L-Glu in the caudal ventrolateral medulla. The profile of the cardiovascular effects elicited by the NPY-related peptides in NTS does not correspond to either of the Y1 or the Y2 receptor subtypes. The findings suggest that NPY acts on an atypical receptor in NTS to lower AP and HR. Moreover, this receptor may also interfere with the L-Glu-evoked neurotransmission in the NTS. Finally, norepinephrine shared with NPY the ability to inhibit L-Glu-evoked responses in NTS; however, a much higher dose of norepinephrine (than NPY) was required.

Animals↗

PubMed1991

Clonidine-displacing substance from bovine brain binds to imidazoline receptors and releases catecholamines in adrenal chromaffin cells.

Identification of nonadrenergic binding sites for clonidine and related imidazolines in brain and peripheral tissues and partial purification of an endogenous ligand for these sites have led to the postulation of a novel transmitter/receptor system. The receptors seem to be present in adrenal medulla and to regulate chromaffin cell function. The present study was undertaken to test the ability of the putative endogenous ligand clonidine-displacing substance (CDS) to displace [3H]idazoxan binding to adrenal chromaffin cell membranes and to release catecholamines from cultured chromaffin cells. CDS potently displaces [3H]idazoxan binding to chromaffin cell membranes, with an IC50 of 5 units. The displacement of [3H]idazoxan binding by CDS was not modified by guanosine 5'-(beta, gamma-imido)triphosphate, suggesting that the imidazoline binding sites may not be GTP-binding protein-coupled receptors. CDS produced a large release of catecholamines from chromaffin cells, and the release was partially blocked by cobalt, a calcium channel blocker. The calcium-dependent release reached a plateau above 5 units of CDS, with a maximal response at 15 min. It is concluded that endogenous CDS, prepared from brain, regulates the secretion of catecholamines from adrenal chromaffin cells, probably by activating imidazole receptors.

Adrenal Medulla↗

PubMed1990

Astrocytes cultured from specific brain regions differ in their expression of adrenergic binding sites.

We sought to characterize regional heterogeneity of astrocytes using adrenergic receptor sites as cellular markers. Primary cultures made from 6 regions of neonatal rat brain consisted almost exclusively of astrocytes. Membranes from astrocytes cultured 1-3 weeks were prepared for radioligand binding assays of beta- and alpha 2-adrenergic sites using the ligands [3H]dihydroalprenolol and [3H]p-aminoclonidine, respectively. Receptor expression was not affected by time in culture. Astrocytes from different brain regions varied up to 3-fold with respect to number but not affinity for both classes of adrenergic binding site with a rank order of cerebral cortex = superior colliculus greater than hippocampus = ventral midbrain greater than or equal to caudate nucleus greater than or equal to hypothalamus. Binding to beta- and alpha 2-adrenergic receptors was positively correlated across brain regions. Astrocytic receptor binding in each region did not correspond to total receptor levels assessed by quantitative autoradiography. We conclude that: (a) astrocytes are markedly heterogeneous between major brain regions with respect to expression of adrenergic binding sites; (b) regional variations in the density of adrenergic binding sites in brain reflect, in part, local specialization of astrocytes; and (c) a substantial proportion of the adrenergic binding sites in some brain regions may be on astrocytes.

Alprenolol↗

PubMed1990

Demonstration of high- and low-affinity beta-adrenergic receptors in slide-mounted sections of rat and human brain.

Studies using isolated cell membranes have shown that beta-adrenergic receptors exist in two interconvertible conformations, one with high affinity for agonists and the other with low affinity. Guanine nucleotides and sodium shift high-affinity receptor sites into low-affinity sites. We sought to demonstrate affinity states of the beta-adrenergic receptor in slide-mounted sections of rat and human postmortem brain, and to determine using quantitative receptor autoradiography the regional distribution in the brain of high-affinity receptors relative to the total population of beta-adrenergic receptors. The beta-adrenergic agonist isoproterenol inhibited the binding of 125I-iodopindolol to slide-mounted sections of rat forebrain and human premotor cortex in a biphasic manner. Approximately 80% of the beta-receptor sites in both rat and human brain showed high-affinity for isoproterenol (7-14 nM). Treatment with 0.1 mM non-hydrolyzable guanine nucleotide 5'-guanylylimidodiphosphate and 25 mM NaCl abolished high-affinity binding in rat brain sections and reduced it in human brain sections. These findings were confirmed by membrane studies using similar tissue samples. For autoradiographic studies, 17 nM isoproterenol displaced 71% of the high-affinity sites without affecting low-affinity beta-adrenergic receptors. Digital subtraction was used to selectively visualize beta-receptors in the high-affinity conformation. The proportion of beta-adrenergic receptors in the high-affinity conformation differed significantly across rat brain regions and across human cortical layers. We conclude that beta-adrenergic affinity states, presumably reflecting the interaction of the receptor with a G-protein, occur in slide-mounted sections of rat brain and persist in human postmortem material.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Synthesis, release and receptor binding of acetylcholine in the C1 area of the rostral ventrolateral medulla: contributions in regulating arterial pressure.

This study sought to determine whether release of acetylcholine (ACh) within the C1 area of nucleus reticularis rostroventrolateralis (RVL) contributes to the tonic maintenance of arterial pressure (AP) in the rat. The activity of choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh, varied 5.5-fold in micropunches of the 6 medullary regions examined. ChAT activity in the C1 area (179 +/- 35 nmol [14C]ACh formed/mg protein/60 min; n = 4) was intermediate between that of the hypoglossal nucleus (249 +/- 38; highest) and the pyramids (45 +/- 11; lowest) and equivalent to that found in the parietal cortex (147 +/- 15). Release of [3H]ACh from C1 area micropunches was increased by raising extracellular K+ concentrations (5-55 mM) and was entirely Ca2(+)-dependent. Muscarinic receptor binding density was assessed using [3H]quinuclidinyl benzylate ([3H]QNB) as ligand and a recently developed 'electronic micropunch' technique which allows measurement of quench-corrected [3H]QNB binding within corresponding cylinders of tissue obtained by the mechanical micropunch cannula. [3H]QNB binding density varied 2.6-fold: lateral reticular nucleus pars lateralis greater than C1 area greater than nucleus ambiguus = hypoglossal nucleus = pyramid = oral spinal trigeminal nucleus. In urethane-anesthetized rats, inhibition of ACh synthesis by hemicholinium-3 (HC-3, 3 nmol/50 nl), or blockade of muscarinic receptors by scopolamine (SCOP, 3 nmol/50 nl), reduced resting mean AP by 18-24 mm Hg following bilateral microinjection into the C1 area. These concentrations of HC-3 and SCOP were sufficient to attenuate by 70-80% the increase in local cholinergic neurotransmission elicited by the cholinesterase inhibitor physostigmine given systemically. High concentrations of SCOP (30-150 nmol/50 nl) lowered AP by 46-60 mm Hg. Similarly, bilateral microinjections of GABA (10 nmol/50 nl) into the C1 area markedly reduced mean AP by 51 +/- 6 mm Hg to levels normally found after transection of the spinal cord. Thus, a substantial portion of tonic sympathetic activity may be driven by activation of muscarinic receptors in the C1 area. In the spontaneously hypertensive rat (SHR), a genetic model of hypertension, neither spontaneous nor K(+)-evoked release of [3H]ACh from the C1 area differed from that of normotensive Wistar-Kyoto rats (WKY).(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1990

Anatomical substrates of cholinergic-autonomic regulation in the rat.

UNLABELLED: Acetylcholine (ACh) plays a major role in central autonomic regulation, including the control of arterial blood pressure (AP). Previously unknown neuroanatomic substrates of cholinergic-autonomic control were mapped in this study. Cholinergic perikarya and bouton-like varicosities were localized by an immunocytochemical method employing a monoclonal antiserum against choline acetyltransferase (ChAT), the enzyme synthesizing ACh. In the forebrain, bouton-like varicosities and/or perikarya were detected in the septum, bed nucleus of the stria terminalis, amygdala (in particular, autonomic projection areas AP1 and AP2 bordering the central subnucleus), hypothalamus (rostrolateral/innominata transitional area, perifornical, dorsal, incertal, caudolateral, posterior [PHN], subparafascicular, supramammillary and mammillary nuclei). Few or no punctate varicosities were labeled in the paraventricular (PVN) or supraoptic (SON) hypothalamic nuclei. In the mid- and hindbrain, immunoreactive cells and processes were present in the nucleus of Edinger-Westphal, periaqueductal gray, parabrachial complex (PBC), a periceruleal zone avoiding the locus ceruleus (LC), pontine micturition field, pontomedullary raphe, paramedian reticular formation and periventricular gray, A5 area, lateral tegmental field, nucleus tractus solitarii (NTS), nucleus commissuralis, nucleus reticularis rostroventrolateralis (RVL), and the ventral medullary surface (VMS). In the PBC, immunoreactive varicosities identified areas previously unexplored for cholinergic autonomic responsivity (superior, internal, dorsal, and central divisions of the lateral subnucleus, nucleus of Koelliker-Fuse and the medial subnucleus). In the NTS, previously undescribed ChAT-immunolabeled cells and processes were concentrated at intermediate and subpostremal levels and distributed viscerotopically in areas receiving primary cardiopulmonary afferents. In the nucleus RVL, cholinergic perikarya were in proximity to the VMS and medial to adrenergic cell bodies of the C1 area. Punctate varicosities of unknown origin and dendrites extending ventrally from the nucleus ambiguus overlapped the C1 area and immediate surround of RVL. IN CONCLUSION: 1) Cholinergic perikarya and putative terminal fields, overlap structures that are rich in cholinoreceptors and express autonomic, neuroendocrine, or behavioral responsivity to central cholinergic stimulation (PHN, NTS, RVL). The role of ACh in most immunolabeled areas, however, has yet to be determined. Overall, these data support the concept that cholinergic agents act at multiple sites in the CNS and with topographic specificity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Lesions of rostral ventrolateral medulla abolish some cardio- and cerebrovascular components of the cerebellar fastigial pressor and depressor responses.

We sought to establish whether the C1 area of the rostral ventrolateral reticular nucleus (RVL) of the medulla oblongata mediates: (1) the elevations in arterial pressure (AP), heart rate (HR) and regional cerebral blood flow (rCBF) elicited by electrical stimulation of the rostral cerebellar fastigial nucleus (FN), the fastigial pressor response (FPR); (2) the reductions in AP and HR elicited by chemical stimulation of intrinsic neurons of FN with excitatory amino acids, the fastigial depressor response (FDR). Studies were conducted on rats anesthetized (chloralose), paralyzed and artificially ventilated. The FN was stimulated electrically through microelectrodes and chemically by microinjection of D.L-homocysteic acid (100 nmol in 100 nl). rCBF was measured in homogenates of 11 brain regions by the 14C-iodoantipyrine technique. Bilateral electrolytic lesions restricted to the RVL abolished the elevations in AP, HR and rCBF elicited by electrical stimulation as well as the fall of AP and HR elicited by chemical stimulation of the FN. The disappearance of the responses was anatomically selective and could not be attributed to changes in resting AP, HR or rCBF, loss of reactivity of preganglionic sympathetic neurons, or variations in blood gases. Since the FN neither projects to nor receives afferents from the RVL the pathway to RVL is indirect. We conclude that: (1) the FPR results from excitation and the FDR inhibition of reticulospinal sympathoexcitatory axons of RVL; (2) the FPR is a consequence of excitation of axons arising from neurons in an as yet unidentified area of lower brainstem projecting to or through the FN and with collateral branches innervating RVL mono- or polysynaptically; (3) the FDR, in contrast, represents excitation of intrinsic FN neurons with a polysynaptic projection to RVL through unidentified regions of lower brainstem; (4) the RVL is a relay mediating the increase in rCBF associated with the FPR; and (5) the RVL plays a critical role in integrating actions on the systemic and cerebral circulation represented in cerebellum.

Animals↗

PubMed1990

Plasma epinephrine modulates the cerebrovasodilation evoked by electrical stimulation of dorsal medulla.

We examined whether plasma epinephrine contributes to the increase in regional cerebral blood flow (rCBF) evoked by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized (alpha-chloralose, 30 mg/kg, s.c.), paralyzed and artificially ventilated. The DMRF was electrically stimulated through microelectrodes stereotaxically implanted. During stimulation, blood gases and arterial pressure were monitored and maintained within normal range. rCBF was determined in 11 dissected brain regions using the [14C]iodoantipyrine technique. Plasma epinephrine and norepinephrine were measured radioenzymatically in rats with intact adrenals or adrenalectomy, and with or without infusion of epinephrine. DMRF stimulation induced widespread increases in rCBF associated with a 50-fold increase in plasma epinephrine and a 20-fold increase in norepinephrine without changes in the electroencephalogram. In contrast, stimulation of the adjacent medial longitudinal fasciculus had no effect upon rCBF or plasma catecholamines. Acute bilateral adrenalectomy produced regionally selective reductions in the stimulation-coupled increases in rCBF throughout brain (P less than 0.05). Infusion of epinephrine in adrenalectomized rats to levels comparable to those observed in intact animals during DMRF stimulation did not by itself modify rCBF. However, when infused in conjunction with stimulation of the DMRF, but not medial longitudinal fasciculus, epinephrine fully restored the stimulus-related increases in rCBF in all brain regions to levels comparable to those observed in intact rats. We conclude that stimulation of the DMRF elevates rCBF through two mechanisms; by a neurally-mediated increase in local metabolism and thereby flow (adrenal independent secondary vasodilation) and by releasing epinephrine from adrenal medulla which secondarily acts to increase rCBF by an action on brain.

Animals↗

PubMed1990

Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims.

Suicidal behavior has been linked to a deficiency in serotonin neurotransmission, but it is not known which brain regions are involved. We determined the pattern of alteration in serotonin 5-HT2 (5-HT2) receptor binding sites in suicide victims in prefrontal cortex compared with temporal cortex using a matched-pairs design to study 11 suicide victims and 11 matched controls, by both membrane binding and quantitative receptor autoradiography. Since a relationship between the serotonergic and noradrenergic systems has been proposed, we also examined beta-adrenergic receptor binding sites. Binding to 5-HT2 and beta-adrenergic sites in slide-mounted sections correlated strongly with binding site number in membrane preparations. A specific laminar distribution of 5-HT2 binding sites was found in both the control and suicide groups, whereas beta-adrenergic binding sites did not differ across cortical layers. A significant increase was found in suicide victims across all cortical layers in both receptor subpopulations in the prefrontal cortex, but only beta-adrenergic sites were increased in the temporal cortex. We conclude that suicide is associated with a localized increase in 5-HT2 binding sites.

Adolescent↗