Biomedical subjects

D M Jacobowitz

Publications and source records attributed to D M Jacobowitz.

At least 325 records · Page 18Linked to original sources

PubMedDate not supplied

Distribution of corticotropin releasing factor-like immunoreactivity in the rat brain by immunohistochemistry and radioimmunoassay: comparison and characterization of ovine and rat/human CRF antisera.

The distribution of corticotropin releasing factor (CRF)-like immunoreactivity in the rat brain has been demonstrated by immunohistochemistry and radioimmunoassay using 4 different antisera. Two antisera were directed against synthetic ovine CRF, two antisera were directed against synthetic rat/human CRF. Immunohistochemistry revealed that there are discrete regions where CRF immunoreactive cell bodies are seen with all 4 antisera (e.g., the paraventricular nucleus, the dorsolateral tegmental nucleus) whereas there are cells observed only with one rat CRF antiserum (e.g., in the cortex) or terminal fields observed only with ovine CRF antisera (e.g., the spinal trigeminal tract, the substantia gelatinosa, the spinal cord). Radioimmunoassay showed different cross reactivity of the antisera with synthetic ovine or rat/human CRF and sauvagine, however, there was no cross reactivity with a variety of other peptides. Tissue values of CRF obtained by RIA of micropunched brain nuclei with the 4 antisera were frequently dissimilar suggesting that different antisera recognize different substances. High performance liquid chromatography and radioimmunoassay of brain tissue samples, revealed that there is more than one form of CRF-like immunoreactivity present. There is indirect evidence that there exists at least one peptide in the rat brain, prominent in the medulla and the spinal cord, which cross reacts with antisera directed to ovine CRF only.

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PubMedDate not supplied

Immunohistochemical mapping of galanin-like neurons in the rat central nervous system.

Using an antiserum generated in rabbits against synthetic galanin (GA) and the indirect immunofluorescence method, the distribution of GA-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system (CNS) and a detailed stereotaxic atlas of GA-like neurons was prepared. GA-like immunoreactivity was widely distributed in the rat CNS. Appreciable numbers of GA-positive cell bodies were observed in the rostral cingulate and medial prefrontal cortex, the nucleus interstitialis striae terminalis, the caudate, medial preoptic, preoptic periventricular, and preoptic suprachiasmatic nuclei, the medial forebrain bundle, the supraoptic, the hypothalamic periventricular, the paraventricular, the arcuate, dorsomedial, perifornical, thalamic periventricular, anterior dorsal and lateral thalamic nuclei, medial and central amygdaloid nuclei, dorsal and ventral premamillary nuclei, at the base of the hypothalamus, in the central gray matter, the hippocampus, the dorsal and caudoventral raphe nuclei, the interpeduncular nucleus, the locus coeruleus, ventral parabrachial, solitarii and commissuralis nuclei, in the A1, C1 and A4 catechaolamine areas, the posterior area postrema and the trigeminal and dorsal root ganglia. Fibers were generally seen where cell bodies were observed. Very dense fiber bundles were noted in the septohypothalamic tract, the preoptic area, in the hypothalamus, the habenula and the thalamic periventricular nucleus, in the ventral hippocampus, parts of the reticular formation, in the locus coeruleus, the dorsal parabrachial area, the nucleus and tract of the spinal trigeminal area and the substantia gelatinosa, the superficial layers of the spinal cord and the posterior lobe of the pituitary. The localization of the GA-like immunoreactivity in the locus coeruleus suggests a partial coexistence with catecholaminergic neurons as well as a possible involvement of the GA-like peptide in a neuroregulatory role.

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PubMedDate not supplied

Calcitonin gene-related peptide: detailed immunohistochemical distribution in the central nervous system.

With the use of an antiserum generated in rabbits against synthetic human calcitonin gene-related peptide (CGRP) the distribution of CGRP-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system. A detailed stereotaxic atlas of CGRP-like neurons was prepared. CGRP-like immunoreactivity was widely distributed in the rat central nervous system. CGRP positive cell bodies were observed in the preoptic area and hypothalamus (medial preoptic, periventricular, anterior hypothalamic nuclei, perifornical area, medial forebrain bundle), premamillary nucleus, amygdala medialis, hippocampus and dentate gyrus, central gray and the ventromedial nucleus of the thalamus. In the midbrain a large cluster of cells was contained in the peripeduncular area ventral to the medial geniculate body. In the hindbrain cholinergic motor nuclei (III, IV, V, VI, VII XII) contained CGRP-immunoreactivity. Cell bodies were also observed in the ventral tegmental nucleus, the parabrachial nuclei, superior olive and nucleus ambiguus. The ventral horn cells of the spinal cord, the trigeminal and dorsal root ganglia also contained CGRP-immunoreactivity. Dense accumulations of fibers were observed in the amydala centralis, caudal portion of the caudate putamen, sensory trigeminal area, substantia gelatinosa, dorsal horn of the spinal cord (laminae I and II). Other areas containing CGRP-immunoreactive fibers are the septal area, nucleus of the stria terminalis, preoptic and hypothalamic nuclei (e.g., medial preoptic, periventricular, dorsomedial, median eminence), medial forebrain bundle, central gray, medial geniculate body, peripeduncular area, interpeduncular nucleus, cochlear nucleus, parabrachial nuclei, superior olive, nucleus tractus solitarii, and in the confines of clusters of cell bodies. Some fibers were also noted in the anterior and posterior pituitary and the sensory ganglia. As with other newly described brain neuropeptides it can only be conjectured that CGRP has a neuroregulatory action on a variety of functions throughout the brain and spinal cord.

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PubMedDate not supplied

Calcitonin gene-related peptide coexists with substance P in capsaicin sensitive neurons and sensory ganglia of the rat.

Immunohistochemical and radioimmunoassay studies revealed that both CGRP- and SP-like immunoreactivity in the caudal spinal trigeminal nucleus and tract, the substantia gelatinosa and the dorsal cervical spinal cord as well as in cell bodies of the trigeminal ganglion and the spinal dorsal root ganglion is markedly depleted by capsaicin which is known to cause degeneration of a certain number of primary sensory neurons. Higher brain areas and the ventral spinal cord were not affected by capsaicin treatment. Furthermore CGRP and substance P-like immunoreactivity were shown to be colocalized in the above areas and to coexist in cell bodies of the trigeminal ganglion and the spinal dorsal root ganglia. It is suggested that CGRP, like substance P, may have a neuromodulatory role on nociception and peripheral cardiovascular reflexes.

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PubMedDate not supplied

Behavioral investigation of the coexistence of substance P, corticotropin releasing factor, and acetylcholinesterase in lateral dorsal tegmental neurons projecting to the medial frontal cortex of the rat.

Colocalization of substance P (SP), corticotropin releasing factor (CRF), and acetylcholinesterase (AChE) was detected by retrograde tracing and immunocytochemical staining in the nucleus tegmentalis dorsalis lateralis (ntdl) projecting to the medial frontal cortex (MFC), septum, and thalamus of the rat. The histochemical results suggest that SP and CRF coexist within a subpopulation of ntdl cholinergic neurons that project to a number of forebrain regions including the MFC. Behavioral studies of the effects of SP, CRF, and the cholinergic agonist, carbachol, employed microinjections into the MFC of rats. SP and CRF did not elicit any behavioral effects when administered alone. Carbachol (1-5 micrograms/side) produced a stereotyped motor behavior, consisting of rapid forepaw treading while in an upright posture, resembling "boxing." SP (1 micrograms/side) increased carbachol-induced "boxing." CRF (1-10 ng/side) decreased carbachol-induced "boxing." One possible functional significance of the coexistence of SP, CRF, and acetylcholinesterase, in neurons projecting to the medial frontal cortex in rats, appears to be a modulatory potentiation of cholinergic response by SP, and a modulatory inhibition of the cholinergic response by CRF.

Acetylcholinesterase↗

PubMedDate not supplied

Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system.

Using autoradiographic method and 125I-Tyro rat CGRP as a ligand, receptor binding sites were demonstrated in the rat central nervous system. Saturation studies and Scatchard analysis of CGRP-binding to slide mounted tissue sections containing primarily cerebellum showed a single class of receptors with a dissociation constant of 0.96 nM and a Bmax of 76.4 fmol/mg protein. 125I-Tyro rat CGRP binding sites were demonstrated throughout the rat central nervous system. Dense binding was observed in the telencephalon (medial prefrontal, insular and outer layers of the temporal cortex, nucleus accumbens, fundus striatum, central and inferior lateral amygdaloid nuclei, most caudal caudate putamen, organum vasculosum laminae terminalis, subfornical organ), the diencephalon (anterior hypothalamic, suprachiasmatic, arcuate, paraventricular, dorsomedial, periventricular, reuniens, rhomboid, lateral thalamic pretectalis and habenula nuclei, zona incerta), in the mesencephalon (superficial layers of the superior colliculus, central nucleus of the geniculate body, inferior colliculus, nucleus of the fifth nerve, locus coeruleus, nucleus of the mesencephalic tract, the dorsal tegmental nucleus, superior olive), in the molecular layer of the cerebellum, in the medulla oblongata (inferior olive, nucleus tractus solitarii, nucleus commissuralis, nuclei of the tenth and twelfth nerves, the prepositus hypoglossal and the gracilis nuclei, dorsomedial part of the spinal trigeminal tract), in the dorsal gray matter of the spinal cord (laminae I-VI) and the confines of the central canal. Moderate receptor densities were found in the septal area, the "head" of the anterior caudate nucleus, medial amygdaloid and bed nucleus of the stria terminalis, the pyramidal layers of the hippocampus and dentate gyri, medial preoptic area, ventromedial nucleus, lateral hypothalamic and ventrolateral thalamic area, central gray, reticular part of the substantia nigra, parvocellular reticular nucleus. Purkinje cell layer of the cerebellum, nucleus of the spinal trigeminal tract and gracile fasciculus of the spinal cord. The discrete distribution of CGRP-like binding sites in a variety of sensory systems of the brain and spinal cord as well as in thalamic and hypothalamic areas suggests a widespread involvement of CGRP in a variety of brain functions.

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PubMedDate not supplied

Effect of calcitonin gene-related peptide on the neuroeffector mechanism of sympathetic nerve terminals in rat vas deferens.

In order to evaluate the mode of action of calcitonin gene-related peptide (CGRP) on the neuroeffector mechanism of peripheral sympathetic nerve fibers, the effects of CGRP were tested on the electrical stimulated and the non-stimulated preparations of the isolated rat vas deferens. The contractile responses, which were mediated predominantly by activation of postganglionic noradrenergic nerve fibers, were dose-dependently inhibited by CGRP in concentrations ranging from 0.1 to 10 nM. The inhibitory response produced by CGRP in high concentrations (greater than 2 nM) usually returned to the control level at 20-30 min and were rarely tachyphylactic. The inhibitory action of CGRP was not modified by pretreatment with 10(-7) M propranolol or 10(-7) M atropine. Contractions produced by exogenous norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in unstimulated preparations were not affected by pretreatment with CGRP in a low concentration (less than 2 nM). On the other hand, the contractions were slightly reduced 1 min after pretreatment with CGRP in high concentrations (greater than 5 nM), which recovered in 15 min after constant flow washout. High concentrations of CGRP also caused a concentration-dependent relaxation on the precontracted preparations produced by high potassium (60 mM K+) solution. These results suggest that CGRP in high concentrations (greater than 5 nM) may have a non-specific inhibitory action on the postsynaptic plasma membrane of the smooth muscle cell and a postulated CGRP receptor exists presynaptically in the rat vas deferens and that CGRP may inhibit the release of NE during adrenergic nerve stimulation.

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PubMedDate not supplied

Increases in heart rate and blood pressure produced by microinjections of atrial natriuretic factor into the AV3V region of rat brain.

Recent studies have provided evidence for the dense localization of atrial natriuretic factor (ANF) in the anteroventral third ventricle (AV3V) region of the rat brain. This area is currently thought to be involved in the regulation of blood pressure and fluid and electrolyte balance. To investigate whether ANF may play a role in central cardiovascular regulation, the effects of microinjection of ANF into the preoptic suprachiasmatic nucleus (POSC), which is located in the AV3V region of the brain, were examined in the present study. Low doses of ANF (2-4 pmol) produced modest elevations in systolic and diastolic pressures, approximately 10-14%, and a small rise in HR of roughly 7%. Higher doses of ANF (20-40 pmol) produced significant increases in systolic (15-19%), mean arterial (12-14%) and pulse (25-36%) pressures. In addition, much larger increases in HR, approximately 20%, were produced by these higher doses of ANF. The onset of effects produced by ANF on BP and HR was seen 15-45 min after injection. Peak effects were usually observed approximately 60-150 min after onset, and the duration of the effect was 2-4 hours, after which time values usually returned to baseline. These studies indicate that ANF produces significant increases in BP and HR when injected at pmol doses into the POSC, and lends support to the idea that this peptide may play an important role in central cardiovascular regulatory mechanisms.

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PubMedDate not supplied

Quantitative distribution of calcitonin gene-related peptide in the rat central nervous system.

Using an antiserum directed against human calcitonin gene-related peptide (hCGRP), which fully cross reacts with rat CGRP, a sensitive radioimmunoassay was developed. The antiserum was characterized by displacement curve characteristics and high performance liquid chromatography. The assay was applied to rat brain tissue and the concentration of CGRP for 48 microdissected brain areas is presented. Highest levels (1000-4500 fmol/mg protein) were found in the central amygdaloid, caudate putamen, and spinal trigeminal nerve nucleus and tract, substantia gelatinosa, and the dorsal horn of the spinal cord. Moderate levels (200-600 fmol/mg protein) were found in the bed nucleus of the stria terminalis, the subfornical organ, the paraventricular, arcuate, dorsomedial, dorsal parabrachial, ambiguus and tractus solitarii nuclei and in the median eminence. These results coincide with those previously obtained by immunohistochemistry. The widespread distribution in the brain suggests involvement of CGRP in a variety of behavioral functions.

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PubMedDate not supplied

Quantitative distribution of galanin-like immunoreactivity in the rat central nervous system.

Using an antiserum directed against synthetic galanin (GAL) a sensitive radioimmunoassay was developed. The antiserum interaction with GAL was characterized by displacement curve characteristics and high performance liquid chromatography. Besides the main GAL-immunoreactive peak several small peaks with GAL-like immunoreactivity were observed. No cross-reactivity of the GAL-antiserum with several other peptides was observed. GAL-like immunoreactivity was measured in 37 microdissected areas of the rat central nervous system. High concentrations (greater than 2000 fmol/mg protein) were observed in the amygdaloid nuclei, the septum, globus pallidus, bed nuclei of the stria terminalis, all hypothalamic nuclei, the superior colliculus, locus coeruleus, the nucleus of the solitary tract and the neurointermediate lobe of the pituitary. Moderate concentrations (1000-2000 fmol/mg protein) were observed in the hippocampus, the nucleus accumbens and nucleus of the diagonal tract, the caudate-putamen, the central gray, the nucleus, tract and substantia gelatinosa of the spinal trigeminal nerve. The results generally correlate with those previously published by immunocytochemistry. The widespread distribution of GAL-like immunoreactivity in the rat central nervous system suggests an involvement of GAL in a variety of brain functions.

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PubMedDate not supplied

Autoradiographic distribution of 125I-galanin binding sites in the rat central nervous system.

Galanin (GAL) binding sites in coronal sections of the rat brain were demonstrated using autoradiographic methods. Scatchard analysis of 125I-GAL binding to slide-mounted tissue sections revealed saturable binding to a single class of receptors with a Kd of approximately 0.2 nM. 125I-GAL binding sites were demonstrated throughout the rat central nervous system. Dense binding was observed in the following areas: prefrontal cortex, the anterior nuclei of the olfactory bulb, several nuclei of the amygdaloid complex, the dorsal septal area, dorsal bed nucleus of the stria terminalis, the ventral pallidum, the internal medullary laminae of the thalamus, medial pretectal nucleus, nucleus of the medial optic tract, borderline area of the caudal spinal trigeminal nucleus adjacent to the spinal trigeminal tract, the substantia gelatinosa and the superficial layers of the dorsal spinal cord. Moderate binding was observed in the piriform, periamygdaloid, entorhinal, insular cortex and the subiculum, the nucleus accumbens, medial forebrain bundle, anterior hypothalamic, ventromedial, dorsal premamillary, lateral and periventricular thalamic nuclei, the subzona incerta, Forel's field H1 and H2, periventricular gray matter, medial and superficial gray strata of the superior colliculus, dorsal parts of the central gray, peripeduncular area, the interpeduncular nucleus, substantia nigra zona compacta, ventral tegmental area, the dorsal and ventral parabrachial and parvocellular reticular nuclei. The preponderance of GAL-binding in somatosensory as well as in limbic areas suggests a possible involvement of GAL in a variety of brain functions.

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PubMedDate not supplied

Cardiovascular effects produced by microinjection of calcitonin gene-related peptide into the rat central amygdaloid nucleus.

Recent studies have provided evidence for a dense localization of calcitonin gene-related peptide (CGRP) and its receptors within the central amygdaloid nucleus (Ce) in rat brain. Since this nucleus has been thought to play a role in central cardiovascular regulation, the present study examined the cardiovascular effects subsequent to the microinjection of CGRP into the Ce. Doses of 50-500 pmol of CGRP produced a significant elevation of 11-15% in systolic, diastolic and mean arterial pressures. Heart rate was significantly elevated by 16-18% by these doses of CGRP. The time course of the effects of CGRP revealed that onset of action occurred after 15-20 min, peak effects were seen at approximately 30-40 min after onset and the effects of the peptide usually lasted for at least 2 hr, after which time BP and HR values returned to baseline. The present study demonstrates that CGRP produces significant increases in both BP and HR when pmol doses of the peptide are injected into the Ce. It is suggested that in the Ce, CGRP plays a neuromodulatory role in cardiovascular function.

Amygdala↗

PubMedDate not supplied

Effects of neuropeptide Y on LH, FSH and TSH release in male rats.

These experiments were undertaken to investigate the effects of systemically administered neuropeptide Y (NPY) on gonadotropin secretion in the intact male rat and to determine whether the effects observed might be mediated by a direct action of NPY alone on the anterior pituitary gland (APG). Subcutaneous administration of 10 micrograms of NPY caused a greater than 2-fold increase in serum luteinizing hormone (LH) concentration at 15 min after injection but was without effect on serum follicle-stimulating hormone (FSH) or thyrotropin-stimulating hormone (TSH) levels. The addition of NPY (final concentrations of 10(-8) to 10(-11) M) or the structurally similar neuropeptide, rat pancreatic polypeptide, to culture medium containing hemi-APG did not alter the release of LH, FSH, or TSH. The results indicate that systemically administered NPY can elevate serum LH concentration in intact male rats. This effect does not appear to be due to NPY acting alone at the level of the APG.

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PubMedDate not supplied

Propranolol and methylatropine antagonize the cardiovascular effects produced by microinjection of the TRH analog MK-771 into the preoptic suprachiasmatic nucleus.

Thyrotropin-releasing hormone (TRH) has been shown to increase heart rate as well as blood pressure when administered into rat brain. The present study investigated the mechanism by which the TRH analog MK-771 produces these effects when injected into the preoptic suprachiasmatic nucleus (POSC). MK-771, at a dose of 125 pmol (50 ng), produced significant increases in both heart rate and blood pressure. These effects occurred within 5 minutes of microinjection and lasted approximately 20-30 minutes. Pretreatment with either the beta-adrenergic antagonist propranolol or the muscarinic antagonist methylatropine, administered into the POSC, significantly altered the response produced by MK-771. Propranolol, at a dose of 7 nmol, and methylatropine at a dose of 0.5 nmol, significantly inhibited the tachycardia produced by MK-771. In addition, methylatropine, at a dose of 0.5 nmol, significantly reduced the increase in diastolic pressure produced by the TRH agonist. These results are consistent with the idea that TRH agonists, when administered centrally, produce cardiovascular alterations through the autonomic nervous system.

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PubMedDate not supplied

Effects of calcitonin gene-related peptide on neuromuscular transmission in the isolated rat diaphragm.

The present study was undertaken to investigate a possible interaction between the cholinergic nerve neurotransmitter and CGRP on neuromuscular transmission in the isolated rat diaphragm. Electrical stimulation of the isolated phrenic nerve resulted in twitch contractions which were dose-dependently potentiated by CGRP in concentrations ranging from 1.2 x 10(-9) M to 3 x 10(-7) M. The potentiating action of CGRP (3 x 10(-7) M) disappeared in about 25 min. The same dose of CGRP 40 min later produced an augmentation of contraction amplitude similar to that observed prior to the administration of CGRP. The action of CGRP was dependent upon the stimulation pulse width ranging from 0.2 to 1.0 msec. Rat calcitonin (4.5 x 10(-7) M) caused a minimal change in the amplitude of twitch contractions. CGRP had no effect on the quiescent striated muscle. Twitch responses to direct electrical stimulation were also enhanced by CGRP (6 x 10(-8) M-6 x 10(-7) M) in the absence and presence of 10(-5) M d-tubocurarine. These results suggest that CGRP modulates the action of acetylcholine at the motor end plates of striated muscle.

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PubMedDate not supplied

Distribution of angiotensin II receptors in the brain of nonhuman primates.

Angiotensin II binding sites were demonstrated at discrete nuclei in the brain of three nonhuman primate species by autoradiography, using the agonist ligand, [Sar1]AII. Although there were some differences in location of the binding sites, all three species exhibited a characteristic pattern of distribution in areas related to water intake, vasopressin secretion, and blood pressure regulation through modulation of sympathetic activity. Studies in the cynomolgus monkey with the antagonist ligand, [Sar1,Ile8]AII, which localizes in pathways as well as nuclei, revealed novel regions of binding including the habenular-interpeduncular pathway, ventral bundle, and XII nerve, in addition to the X nerve. These data indicated that AII, as in other species, has a role in the central homeostatic control mechanisms in the primate.

Angiotensin II↗

PubMedDate not supplied

Identification and distribution of alpha-melanotropin in discrete regions of the cat brain.

The distribution of alpha-melantropin-like material (alpha-MSH) was demonstrated in rat brain using a microdissection technique combined with radioimmunoassay. Highest concentrations of alpha-MSH were noted in the hypothalamus and preoptic area. Particularly high concentrations were observed in the arcuate nucleus, median eminence, suprachiasmatic nucleus, periventricular nucleus and the medial preoptic nucleus. The thalamic paraventricular nucleus also contained high alpha-MSH concentrations. Moderate to low concentrations were noted in other thalamic, septal, amygdaloid and midbrain nuclei. Low concentrations were observed in cortical and striatal regions.

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PubMedDate not supplied

Effects of ovarian hormones on levels of luteinizing hormone in plasma and on serotonin concentrations in discrete brain nuclei.

Levels of serotonin were measureed in microdissected, individual brain nuclei in ovariectomized rats after treatment with ovarian hormones. Regions sampled included nuclei in the forebrain, rostral and medial hypothalamus, and midbrain tegmentum. Estradiol benzoate decreased levels of luteinizing hormone in plasma but did not affect serotonin levels in any region. Progesterone alone elevated serotonin content in the nucleus tractus diagonalis and ventral tegmental area. The combined estrogen plus progesterone regime produced a surge in plasma luteinizing hormone and also markedly elevated serotonin in the median eminence. These results may be of significance for ovarian hormonal regulation of gonadotropin secretion and reproductive behavior.

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