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D M Jacobowitz

Publications and source records attributed to D M Jacobowitz.

At least 163 records · Page 9Linked to original sources
PubMed1984

Primate model of Parkinson's disease: alterations in multiple opioid systems in the basal ganglia.

A motor disorder similar to idiopathic Parkinson's Disease develops in rhesus monkeys after several daily repeated doses of N-methyl-4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP). The concentrations of peptides derived from proenkephalin A, proenkephalin B, substance P and somatostatin were measured by specific radioimmunoassays in the basal ganglia of MPTP-treated monkeys. In MPTP-treated monkeys, dynorphin B concentration was reduced in the caudate. In the putamen, the concentrations of peptides derived from both proenkephalin A and proenkephalin B were decreased. In the globus pallidus, the concentrations of all opioid peptides tend to be increased, reaching significance only for alpha-neo-endorphin. In the substantia nigra, only Met-enkephalin concentration was reduced, while other peptides derived from either proenkephalin A or proenkephalin B were not changed. Substance P and somatostatin were not changed in any brain area examined. Some of the symptoms associated with Parkinson's Disease may be related to altered activity of endogenous opiates in basal ganglia.

Animals↗
PubMed1984

The subnuclear distribution of substance P, cholecystokinin, vasoactive intestinal peptide, somatostatin, leu-enkephalin, dopamine-beta-hydroxylase, and serotonin in the rat interpeduncular nucleus.

The distribution of immunofluorescent somata and processes within the interpeduncular nucleus (IPN) containing substance P (SP), cholecystokinin (CCK), vasoactive intestinal peptide (VIP), somatostatin (SST), leu-enkephalin (L-ENK), dopamine beta hydroxylase (DBH), and serotonin (5HT) was examined in male rats treated with colchicine 48 hours prior to perfusion. Serial sections were examined for immunofluorescence and variations in the density of fluorescence rated 1 + (sparse) to 4 + (dense). The rostral subnucleus contained SP, SST, and L-ENK-positive somata and processes. Substance P and VIP processes were present throughout the rostral subnucleus but were concentrated in two ovoid areas located dorsally in the caudal region of this subnucleus. Cholecystokinin and L-ENK processes surrounded these ovoid areas. The entire width of the central subnucleus was crossed by SP and L-ENK processes oriented horizontally in narrow bands. Substance P processes were also aligned into vertical columns adjacent to the lateral margins of the central subnucleus. Leu-enkephalin and 5HT processes were distributed throughout this subnucleus, while VIP processes were present only caudally. Dopamine beta hydroxylase processes were evenly distributed but were restricted from the vertical columns laterally. The intermediate subnuclei contained a sparse density of SP and 5HT processes that were present in proximity to the major blood vessels penetrating this subnucleus. Only DBH processes were evenly distributed. The lateral subnuclei contained a dense concentration of SP processes. The medial edges of this subnucleus were distinguished by VIP, CCK, L-ENK, and 5HT processes. The dorsal subnucleus contained 5HT, L-ENK, and SST-positive somata and processes. Substance P, VIP, CCK, and DBH processes were also present. Dorsal-lateral subnuclei contained SP, SST, L-ENK, and DBH processes. Interstitial subnuclei contained SP, CCK, L-ENK, 5HT, and DBH processes. This study demonstrates that perikarya and processes containing peptides and monoamines are distributed within subnuclei of IPN in a topographic and heterogeneous pattern. New features of IPN organization are revealed.

Animals↗
PubMed1984

Increases in heart rate and blood pressure produced by injections of dermorphin into discrete hypothalamic sites.

Central cardiovascular sites of action for dermorphin were determined by injecting 40 pmol of the peptide into discrete sites within the hypothalamus of halothane anesthetized rats. Blood pressure and heart rate in 101 rats were 88 +/- 1 mm Hg and 338 +/- 3 beats/min, respectively, prior to 100 nl intrahypothalamic injections of either vehicle or dermorphin. In the caudal anterior hypothalamic nucleus (A5800-5300), dermorphin, but not vehicle, increased blood pressure 8% and heart rate 26%, without changing respiration rate. The peak response was at 32 +/- 5 min, the duration greater than 90 min. Injections of naloxone (30 nmol) into the same anterior hypothalamic site, or 3 mg/kg naloxone administered i.m., completely reversed the cardiovascular actions. Similar increases in heart rate and blood pressure occurred at A6600-6300, the region between medial preoptic and anterior hypothalamic nuclei. Small increases in heart rate, but not blood pressure, resulted from dermorphin injections into the septal area, medial preoptic nucleus, paraventricular hypothalamic nucleus and the lateral ventricle, while injections in the posterior and dorsomedial hypothalamic nuclei were without effect on blood pressure and heart rate. These data provide support for anterior hypothalamic and medial preoptic sites for the cardiovascular actions of the opiate receptor agonist, dermorphin, and indicate greatest effects with this dose (primarily on heart rate) are produced at discrete sites (A6600-6300 and A5800-5300) within these nuclei.

Animals↗
PubMed1984

Effects of adrenalectomy, propranolol and methylatropine on the increase in heart rate induced by injection of dermorphin in the rat anterior hypothalamic nucleus.

Anterior hypothalamic injections of 40 pmol dermorphin, a potent opiate receptor agonist, increased heart rate 17% and had no effect on blood pressure in halothane-anesthetized rats. Administration of the beta-receptor antagonist, propranolol, during the peak response to dermorphin, reduced the heart rate to levels not different from pretreatment control; pretreatment with propranolol completely blocked the tachycardia produced by a subsequent injection of dermorphin. In contrast, neither adrenalectomy nor pretreatment with methylatropine altered the response to dermorphin. These data suggest that increased activity of the sympathetic nervous system, primarily to the heart, and not increased release of adrenal catecholamines or inhibition of parasympathetic nervous system activity, is responsible for the increase in heart rate resulting from injection of dermorphin into the anterior hypothalamic nucleus.

Adrenalectomy↗
PubMed1984

Phenylethylamine, norepinephrine and mounting behavior in the male rat.

Phenylethylamine, which induces mounting behavior in naive adult male rats when administered chronically, was shown to selectively raise brain norepinephrine levels in the medial preoptic nucleus, a region known to be implicated in the regulation of sexual behaviors. It is suggested that the catecholamine alteration is a secondary response to the primary influence of phenylethylamine on the preoptic nucleus.

Animals↗
PubMed1984

A study of afferent projections to the rat interpeduncular nucleus.

Forebrain and brainstem afferents projecting to the interpeduncular nucleus (IPN) have been demonstrated in male rats by retrograde transport of fluorescent dye, "fast blue," microinjected in IPN, followed by intraventricular colchicine 48 hr prior to perfusion. The most intensely labeled cells projecting to IPN were concentrated throughout the entire rostrocaudal extent of the medial habenular nuclei. A small number of labeled medial habenular cells located dorsomedially also revealed SP immunofluorescence. Additional forebrain afferents originate from septal, hypothalamic and mammillary nuclei. Of brainstem afferents projecting to IPN, the most intensely labeled neurons were present in a circumscribed region overlying the dorsal aspect of the dorsal tegmental nucleus, an area described in the cat as the nucleus incertus [5], and which we now suggest is present in the rat. Many labeled cells in the medial aspect of this nucleus also revealed L-ENK immunofluorescence. Additional brainstem afferents include the raphe, dorsolateral tegmental nuclei and locus coeruleus. This study demonstrates both forebrain and brainstem afferents projecting to IPN and reveals an SP and L-ENK projection from the medial habenula and nucleus incertus, respectively.

Afferent Pathways↗
PubMed1984

Cardiovascular effects of discrete intrahypothalamic and preoptic injections of bradykinin.

Blood pressure and heart rate were monitored during discrete injections of bradykinin (5 nmol; 100-300 nl) in the hypothalamus and preoptic area of halothane anesthetized rats. In the paraventricular nucleus, bradykinin produced bradycardia without effecting blood pressure. The decrease in heart rate was abolished by pretreatment with methylatropine (IP), suggesting that the parasympathetic nervous system mediates this response. In contrast, in the dorsomedial and posterior hypothalamic nuclei, bradykinin increased both heart rate and blood pressure; methylatropine pretreatment (but not adrenalectomy) blocked these responses, suggesting that inhibition of the parasympathetic nervous system is responsible for the actions of bradykinin in these nuclei. In the preoptic suprachiasmatic nucleus, bradykinin produced an increase in heart rate only, which was attenuated by either methylatropine or adrenalectomy, indicating that both inhibition of the parasympathetic nervous system and adrenal catecholamine release contribute to the actions of bradykinin at this site. The increase in heart rate observed with bradykinin in the medial preoptic and anterior hypothalamic (A6400-6001 region) nuclei was not effected by either methylatropine or adrenalectomy, therefore activation of the sympathetic nervous system may be involved in responses in these regions. Finally, a 5 nmol dose of bradykinin potentiating factor (converting enzyme inhibitor; CEI) had effects similar to bradykinin when injected into the posterior hypothalamus, but no effect at any other brain site. CEI administration into brain sites 15 min prior to bradykinin injections failed to alter the bradykinin response. In summary, the central cardiovascular responses to bradykinin depend upon the specific site of injection and these sites correspond with the localization of bradykinin-like immunoreactivity previously reported by others.

Adrenalectomy↗
PubMed1984

Corticotropin releasing factor-like immunoreactive neurons in the rat retina.

Corticotropin releasing factor (CRF)-like immunoreactive neurons have been identified in the rat retina by immunohistochemical methods using antisera directed against ovine and rat CRF. CRF-like immunoreactivity was observed in both amacrine and ganglion cells which projected fine varicose processes to the inner plexiform layer of the retina. It is suggested that CRF may play a role in retinal function.

Animals↗
PubMed1984

Localization of substance P, acetylcholinesterase, muscarinic receptors and alpha-bungarotoxin binding sites in the rat interpeduncular nucleus.

On the basis of acetylcholinesterase (AChE) staining, the rat interpeduncular nucleus was subdivided into five distinct zones. Intense AChE staining was observed in the dorsal cap and the lateral zones. Moderate staining was seen in the median zone and the dorsoventral column. The perivascular zones were unlabeled. Adjacent sections were stained for AChE and for substance P immunofluorescence. Substance P like immunoreactivity was found to coincide with the localization of AChE in the dorsal cap and the lateral zones. Both muscarinic receptors and alpha-bungarotoxin binding sites had distributions resembling that of AChE. Neither unilateral nor bilateral lesions of the habenulae changed the number or distribution pattern of the receptors. It was concluded that cholinergic receptors are localized postsynaptically. Our study suggests AChE and substance P containing fibers terminate in well defined zones of the interpeduncular nucleus which also contain muscarinic and nicotinic receptors.

Acetylcholinesterase↗
PubMed1984

Capsaicin depletes corticotropin-releasing factor-like immunoreactive neurons in the rat spinal cord and medulla oblongata.

Treatment of newborn rats with capsaicin was shown to cause a disappearance of corticotropin-releasing factor immunoreactive nerve fibers in the dorsal horn of the spinal cord (laminae I and II), the spinal trigeminal nucleus and tract, and the nucleus tractus solitarius, but not in the median eminence and the nucleus amygdaloideus centralis. Since it is well known that capsaicin acts selectively on primary sensory neurons of the C-fiber type, it is suggested that corticotropin-releasing factor is also located in peripheral sensory neurons, representing a novel peptidergic neuronal system, possibly involved in the modulation or transmission of peripheral nociceptive impulses, which is different from the capsaicin-resistant hypothalamoinfundibular corticotropin-releasing factor system.

Animals↗
PubMed1984

Effect of desmethylimipramine and reserpine on the concentration of specific proteins in the parietal cortex and the hippocampus of rats as analyzed by two-dimensional gel electrophoresis.

The effect of desmethylimipramine (DMI) and reserpine on the concentration of specific proteins in the parietal cortex and the hippocampus of rats was assessed using two-dimensional gel electrophoresis combined with computer-assisted scanning densitometry. Chronic administration of DMI for 3 weeks was found to produce a significant reduction in the concentration of two proteins in both brain regions examined. Both of these proteins have a molecular weight of approximately 57,000 daltons and isoelectric point of 6.2 to 6.3. A third, smaller protein (MW 28,000 daltons, isoelectric point 5.9) was increased in concentration in rats treated repeatedly with DMI. Acute drug treatment was, in all three cases, found to be without effect. In contrast, chronic treatment of rats with reserpine produced effects on these three proteins in the hippocampus which were quantitatively opposite to those obtained after chronic DMI administration. Again, acute drug treatment was without effect. These results demonstrate that chronic, but not acute, administration of agents affecting noradrenergic reactivity can also have an effect on the concentration of specific proteins within the central nervous system and are of interest in view of the known effects of these drugs on neurotransmitter and enzyme systems in the central nervous system.

Animals↗
PubMed1984

Proteins in normal, irradiated, and postmortem human brain quantitatively compared by using two-dimensional gel electrophoresis.

Using a combination of two-dimensional gel electrophoresis (2DE), silver staining, and computerized densitometry, we studied protein patterns in human cerebral cortex: normal fresh-frozen, fresh-frozen but previously irradiated, and post-mortem. The relative molecular mass of the resolved proteins ranged from 14 400 to 100 000, the isoelectric points from 4.75 to 7.0. The pattern of proteins (six of them identified) was essentially the same for all three groups. However, computerized densitometry demonstrated significant alterations in the density of several spots in the irradiated and postmortem groups as compared with the normal controls. Irradiated cortex showed statistically significant changes in only six spots (three increased and three decreased in density); postmortem material showed 20 altered spots (16 diminished and four increased). Evidently normal human cerebral cortex has a consistent protein pattern on 2DE, which is quantitatively (but not qualitatively) altered in irradiated and postmortem material. These findings provide a point of reference against which proteins from abnormal brain material can be compared, both qualitatively and quantitatively.

Cerebral Cortex↗
PubMed1984

Two-dimensional gel electrophoresis used in neurobiological studies of proteins in discrete areas of the rat brain.

Using two-dimensional gel electrophoresis, we studied proteins in the rat brain. The relative amounts of individual proteins differ in discrete areas of the brain, and the concentrations of three different proteins can be altered by chronic administration of desmethylimipramine or reserpine. Brain proteins can be radiolabeled in vitro by incubating samples of fresh tissue with [35S]methionine. We identified several proteins by using immunoblotting and comigration. Finally, we developed a possible animal model for studying proteins related to Alzheimer's disease by depleting the cholinergic innervation to the cortex and the hippocampus.

Animals↗
PubMed1983

Cardiovascular effects of intrahypothalamic injections of alpha-melanocyte stimulating hormone.

Injection of alpha-melanocyte stimulating hormone (alpha-MSH, 0.6-1.2 nmol in 100-300 nl) into the rostral dorsomedial hypothalamic nucleus of the halothane anesthetized rat resulted in a 12% increase in heart rate (41 +/- 4 bpm) which was accompanied by a slight increase in blood pressure (5 +/- 1 mm Hg). The response was characterized by a gradual onset, with a peak increase at 7 +/- 1 min and a duration of 51 +/- 6 min. Tachyphylaxis to the response was apparent for at least 180 min following initial exposure to the peptide. In contrast to the increase in heart rate observed following alpha-MSH injection into the dorsomedial nucleus, injections into the medial preoptic, anterior, paraventricular or posterior hypothalamic nuclei had no significant effects on blood pressure and heart rate. These data suggest a possible role for brain alpha-MSH in the central control of heart rate at a site within the dorsomedial nucleus of the hypothalamus.

Animals↗
PubMed1983

Vasoactive intestinal polypeptide immunoreactive and cholinergic nerves in the whole mount preparation of the major cerebral arteries of the rat.

An immunofluorescence histochemical study of vasoactive intestinal polypeptide (VIP) was made in the major rat cerebral arteries of the whole mount preparation. A comparison was made between the distribution of VIP-immunoreactive and cholinergic nerves. An abundant number of VIP-containing nerves were observed in the internal carotid, anterior cerebral, middle cerebral and basilar artery. VIP and cholinergic nerves were unaffected by bilateral superior cervical ganglionectomy. The density and distribution of VIP-immunoreactive fibers was essentially the same as that of the cholinergic fibers of the rat cerebral vasculature. It is suggested that, as was previously demonstrated in other peripheral organs, VIP coexists within cholinergic neurons of the rat cerebral arteries.

Animals↗