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M C Beinfeld

Publications and source records attributed to M C Beinfeld.

At least 91 records · Page 5Linked to original sources
PubMed1985

Cholecystokinin innervation of the ventral striatum: a morphological and radioimmunological study.

Immunocytochemistry, radioimmunological assay after surgical cuts, anterograde degeneration and retrograde tracing of fluorescent dyes were used in order to elucidate the cholecystokinin-containing afferents to the ventral striatum (nucleus accumbens, olfactory tubercle and ventral part of the caudate-putamen). In agreement with the report by Hökfelt et al., midbrain cholecystokinin-containing cells supply the posteromedial parts of the nucleus accumbens and olfactory tubercle, as well as the subcommissural part of caudate-putamen. Brainstem cholecystokinin afferents also reach more rostral parts of the ventral striatum including the rostrolateral olfactory tubercle. The ascending cholecystokinin axons enter the medial forebrain bundle at the meso-diencephalic border and maintain a rough medial to lateral topography at the caudal diencephalon. A second major cholecystokinin pathway, with possible origin in the piriform and medial prefrontal cortices and/or the amygdala, projects to the subcommissural caudate-putamen, the olfactory tubercle, the lateral part of the nucleus accumbens and the dorsal part of the bed nucleus of stria terminalis. Finally, the rostral part of the dorsal caudate-putamen receives a substantial cholecystokinin innervation from the basolateral amygdala and possibly from the neocortex. According to radioimmunological data, the descending telencephalic cholecystokinin system accounts for about 60% of all cholecystokinin in the rostral forebrain. The combined use of morphological and biochemical methods provided evidence for a partially overlapping distribution and possible interaction between an ascending brainstem and descending telencephalic cholecystokinin fiber systems within the striatum and related rostral forebrain areas.

Animals↗
PubMed1985

The distribution of cholecystokinin-8 in the central nervous system of turtles: an immunohistochemical and biochemical study.

Immunohistochemical techniques, radioimmunoassay (RIA) and high performance liquid chromatography (HPLC) were used to: (1) determine the regional distribution and amounts of cholecystokinin-8 (CCK8)-like immunoreactivity in the turtle central nervous system, and (2) chemically characterize the CCK8-like material present in the turtle central nervous system. High levels of CCK8-like immunoreactivity were found in the turtle central nervous system, with the highest levels being present in the hypothalamus and neurohypophysis. Moderate levels of the CCK8-like material were found in all other regions of the turtle nervous system except the cerebellum, the olfactory bulbs and the dorsal ventricular ridge of the telencephalon, which contained low levels. The bulk (87%) of the CCK8-like material in turtle central nervous system co-eluted with CCK8-sulfate in gradient elution HPLC. The distribution of CCK8-like immunoreactivity (CCK8LI) observed using immunohistochemistry was consistent with the results of the RIA studies. Numerous CCK8LI-containing neurons and fibers were observed in the hypothalamus and neurohypophysis. Neurons and fibers containing CCK8 were, however, more sparsely distributed outside the hypothalamus. The immunohistochemical data provided evidence for the existence of two major CCK8-containing pathways in turtles that have been previously described in mammals: a pathway from the supraoptic and paraventricular magnocellular nuclei to the external zone of the median eminence and neurohypophysis and a pathway from dorsal root ganglia to the dorsal horn of the spinal cord. Overall, the present results, in conjunction with several previous studies, indicate that CCK8 has had a relatively stable evolutionary history as a CNS neuropeptide among land vertebrates. The molecular structure of CCK8 appears to have been largely (if not entirely) conserved, as has its concentration in many brain regions. A noteworthy exception to such conservatism in the localization of CCK8 is that the concentration of CCK8 in the telencephalon, particularly in the telencephalic cortex, is much lower in turtles than in mammals. The present results therefore suggest that CCK8 may not have become a prominent peptide in the telencephalic cortex (or its anatomical equivalents) until the evolution of neocortex in the mammalian lineage.

Animals↗
PubMed1985

The subcellular distribution of peptide histidine isoleucine amide-27-like peptides in rat brain and their release from rat cerebral cortical slices in vitro.

The subcellular distribution of peptide histidine isoleucine amide (PHI)-27-like peptides (PLP) was investigated in rat cerebral cortex and whole rat brain in comparison with the distribution of vasoactive intestinal peptide (VIP). The highest content of PLP was found in the crude mitochondrial fraction (P2) and was also detected in the microsomal pellet. PLP was recovered in synaptosomes when further fractionation of P2 was performed. This distribution of PLP closely follows that of VIP and is suggestive of possible storage in vesicles at the nerve terminal. Basal release of PLP from rat cerebral cortical slices was below the detection limit of the PHI radioimmunoassay. However, depolarization by 55 mM potassium induced measurable PLP release. This release was calcium-dependent. These findings support the hypothesis that PLP could play a role in neurotransmission.

Animals↗
PubMed1985

Specific regulation of vasoactive intestinal polypeptide biosynthesis by phorbol ester in bovine chromaffin cells.

Two neuropeptides, enkephalin and vasoactive intestinal polypeptide (VIP), are simultaneously increased in cultures of bovine chromaffin cells after diverse treatments including elevation of cAMP, application of nicotine, or chronic depolarization. We now show that phorbol esters can specifically elevate VIP in cultured chromaffin cells without changing the amount of enkephalin. Peptide histidine isoleucine, a VIP-related peptide, is also expressed concomitantly with VIP after treatment with phorbol ester. Immunocytochemical examination of drug-treated cells defines a subpopulation of chromaffin cells which are responsive to phorbol ester stimulation. The unique ability of phorbol esters to selectively regulate VIP expression indicates the presence of independent mechanisms for controlling the expression of individual neuropeptides in chromaffin cells.

Animals↗
PubMed1985

The co-occurrence of a substance P-like peptide and cholecystokinin-8 in a fiber system of turtle cortex.

Single-label and double-label immunohistochemical techniques were used to demonstrate the coexistence of substance P-like immunoreactivity (SPLI) and cholecystokinin-8-like immunoreactivity (CCK-8-LI) in an extensive fiber system within the telencephalic cortex of turtle. All SPLI-containing fibers and terminals of this system contain CCK-8-LI and vice versa. The fibers of this system course from more medial cortical regions to more lateral ones, originating either from neurons in the more medial cortices or from extracortical neurons, the axons of which ascend the medial wall of the cortex. The precise location of the neurons that give rise to this cortical projection system is uncertain, but a hypothalamic location seems most likely at present. The fibers and terminals of this system are found throughout the entire mediolateral and rostrocaudal extent of the telencephalic cortex of turtle and are largely confined to the cell body layer of the cortex. Fewer SPLI/CCK-8-LI-containing fibers are found in pyriform (olfactory) cortex than in the other cortices. Ultrastructural studies indicate that SPLI/CCK-8-LI-containing terminals make asymmetric synapses on cell bodies or their proximal dendrites. Both SPLI and CCK-8-LI are found in large dense core vesicles in these labeled terminals. Labeled terminals also contained numerous small, round, unlabeled vesicles clustered near synaptic release sites and a number of unlabeled large dense core vesicles. Quantification of the percentage of the large dense core vesicles that were labeled in SP-labeled terminals, in CCK-8-labeled terminals, and in terminals labeled for both SP and CCK-8 provided suggestive evidence that SPLI and CCK-8-LI must be contained within the same large dense core vesicles. Radioimmunoassay indicated that the SP/CCK-8-containing system of turtle cortex contains 0.93 +/- 0.090 pg of SP/microgram of cortical tissue protein and 0.31 +/- 0.11 pg of CCK-8/micrograms of cortical tissue protein. The CCK-8-like material in turtle cortex coelutes with CCK-8-sulfate, using gradient elution high pressure liquid chromatography (HPLC). The SP-like material, although immunologically highly similar to undecapeptide SP (Reiner, A., J. E. Krause, K. T. Keyser, W. D. Eldred, and J. F. McKelvy (1984) J. Comp. Neurol. 226: 50-75), does not coelute with undecapeptide SP using gradient elution HPLC.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

The regional distribution and the chemical, chromatographic, and immunologic characterization of motilin brain peptides: the evidence for a difference between brain and intestinal motilin-immunoreactive peptides.

Motilin-like immunoreactive peptides (MLIPs) have been detected in the brain by radioimmunoassay (RIA), (Yanaihara, C., H. Sato, N. Yanaihara, S. Naruse, W. G. Forssman, V. Helmstaedter, T. Fujita, K. Yamaguchi, and K. Abe (1977) Adv. Exp. Biol. Med. 106: 269-283; Chey, W. Y., R. Escoffery, F. Roth, T. M. Chang, and H. Yajima (1980) Regul. Pept. Suppl. 1: 519; O'Donohue, T. L., M. C. Beinfeld, W. Y. Chey, T. M. Chang, G. Nilaver, E. A. Zimmerman, H. Yajima, H. Adachi, M. Roth, R. P. McDevitt, and D. M. Jacobowitz (1981) Peptides 2: 467-477). Previous studies (O'Donohue et al., 1981) demonstrated that MLIPs in rat brain probably differ chemically from porcine intestinal motilin (PIM), the first motilin peptide isolated. The possibility that this rat-pig difference represents a species difference was not examined in the previous study (O'Donohue et al., 1981), neither was the question of the cross-species distribution of MLIP. This study was initiated to examine brain MLIP distribution by RIA in three additional species: cow, pig, and guinea pig. The question of rat-pig species differences was addressed by characterizing MLIP in the brains of these species in comparison to PIM. By RIA, MLIPs were widely distributed in the brains of all species examined. MLIP concentration was highest in rat brain and lowest in pig brain. Some motilin antisera consistently detected less or no MLIPs in some brain regions of all species. Rat pituitary, pineal gland, and retina had substantially higher MLIP concentrations than did brain. MLIPs were abundant throughout the rat gastrointestinal tract and in some other peripheral organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

An overview of the biochemistry and anatomy of cholecystokinin (CCK) peptides in the brain.

In the nine years that have passed since the discovery of CCK in the brain, we have learned much about its biochemistry and anatomy. The anatomy of CCK in the brain is complex and in some instances does not fit with classical anatomical concepts. It is apparently common for some brain structures to have multiple CCK innervation and for interneurons and possible projection neurons to be present in the same structures, which may also receive afferent CCK input. Much work needs to be done before we completely understand the biochemistry, anatomy and function of CCK in the brain.

Animals↗
PubMed1984

The development of motilin-like immunoreactivity in the rat cerebellum and pituitary as determined by radioimmunoassay.

Motilin-like immunoreactivity (MLI) was determined in cerebelli and pituitaries of the rat from 4 days before birth to about 6 months after. Cholecystokinin (CCK)-like immunoreactivity was measured in the same pituitary samples for comparison. MLI concentration was highest 4 days prenatally in both tissues, while total tissue MLI content was higher after birth. Cerebellar MLI content was maximal from day 14 to 40, while pituitary MLI content increased gradually with age, roughly paralleling the increase in tissue protein. Pituitary CCK was detectable only postnatally; its concentration was maximal between days 19 and 29, and decreased substantially in older animals. The presence of detectable MLI in pituitary before birth is consistent with the observation that MLI can be visualized by immunocytochemistry in anterior pituitary somatotrophic cells, which are known to be active producers of growth hormone before and after birth. The presence of MLI before birth in cerebellum is consistent with the localization of MLI in Purkinje neurons, known to be formed before birth. The presence of MLI in the cerebellum before birth and its marked increase in content during the period of synaptogenesis are suggestive of a possible role of motilin in development.

Aging↗
PubMed1984

Brainstem projection to the hypothalamic ventromedial nucleus in the rat: a CCK-containing long ascending pathway.

In order to identify the source and topography of cholecystokinin-containing fibers innervating the hypothalamic ventromedial nucleus (VMN), radioimmunoassay, immunocytochemistry, retrograde tracing of horseradish peroxidase and anterograde degeneration techniques were used. Cholecystokinin (CCK) disappeared almost totally from the VMN following a caudal diencephalic knife cut, which transected the medial fibers of the internal capsule, and the dorsolateral portion of the medial forebrain bundle at the level of the mammillary body. A number of cells in the ipsilateral dorsal parabrachial nucleus, furthermore, showed intense CCK-like immunoreactivity. The ascending CCK-containing fibers in the lateral part of the medial forebrain bundle reach the VMN from the lateral side. Neither the fibers of the stria terminalis, nor of the medial corticohypothalamic tract seem to carry any significant amount of CCK to the VMN.

Afferent Pathways↗
PubMed1984

Cholecystokinin in the hypothalamo-hypophyseal system.

Immunohistochemical studies on cholecystokinin-like (CCK-ir) substances in colchicine-pretreated rats demonstrated that in addition to CCK-ir cells in the magnocellular portion of the paraventricular nucleus. CCK-ir cells are also present among the parvocellular neurons. Radioimmunoassay of CCK after paraventricular lesions indicate that most, if not all, of the CCK in the posterior pituitary and in the median eminence originates from the paraventricular nucleus. It appears that CCK-fibers, like other neuropeptidergic fibers from the paraventricular nucleus (vasopressin, oxytocin, TRH, CRF) enter the medial basal hypothalamus through a common gate--the lateral retrochiasmatic area--in traveling to the median eminence.

Animals↗
PubMed1984

Failure of chronic haloperidol treatment to alter levels of cholecystokinin in the rat brain striatum and olfactory tuberclenucleus accumbens area.

We have studied the effect of chronic haloperidol (HAL) treatment on CCK-8 levels in two rat brain regions. HAL administration using two different protocols, daily injections and infusion with subcutaneously implanted minipumps, did not produce any significant changes in CCK-8 levels in the striatum or olfactory tubercle-nucleus accumbens area.

Animals↗
PubMed1984

Secretin receptors on neuroblastoma cell membranes: characterization of 125I-labeled secretin binding and association with adenylate cyclase.

Secretin, a gut-brain peptide, elicited cyclic AMP production in a clone of neuroblastoma cells derived from the C1300 mouse tumor. Adenylate cyclase (EC 4.6.1.1) in plasma membranes from these cells was stimulated by secretin greater than vasoactive intestinal peptide greater than peptide histidine isoleucine amide, but not by the related peptides glucagon, gastric inhibitory polypeptide, or human growth hormone releasing factor. Hill coefficients for stimulation approximated one and the response to submaximal peptide concentrations was additive, as expected for hormones competing for a single receptor associated with the enzyme. Binding of 125I-labeled secretin to the neuroblastoma plasma membranes was saturable, time-dependent, and reversible. The KD determined from kinetic and equilibrium binding studies approximated 1 nM. The binding site displayed marked ligand specificity that paralleled that for stimulation of adenylate cyclase. The secretin receptor was regulated by guanine nucleotides, with guanosine 5'-(beta, gamma-imino)-triphosphate being the most potent to accelerate the rate of dissociation of bound secretin. These findings demonstrate the functional association of the secretin receptor with adenylate cyclase in neuronally derived cells.

Adenylyl Cyclases↗
PubMed1984

The distribution and chromatographic characterization of PHI (peptide histidine isoleucine amide)-27-like peptides in rat and porcine brain.

This study was initiated to characterize PHI (peptide histidine isoleucine amide)-27-like peptides (PLPs) in rat and porcine brain in comparison with other members of the vasoactive intestinal polypeptide (VIP) family and to investigate their distribution by radioimmunoassay. The peptidic nature of the rat brain PLP was indicated by its trypsin sensitivity. On Sephadex chromatography rat brain PLP has the same molecular weight as synthetic (porcine intestinal) PHI-27. High pressure liquid chromatographic separations revealed that PLP in rat and porcine brain extracts elutes as a single peak distinct from VIP or secretin. Porcine brain PLP elutes in the same position as synthetic PHI-27, whereas rat brain PLP immunoreactivity consistently separates from synthetic PHI-27. This suggests that porcine brain PLP is identical to synthetic PHI-27, in agreement with the reported sequence of Tatemoto et al. (Tatemoto, K., M. Carlquist, T. McDonald, and V. Mutt (1983) FEBS Lett. 153: 248-252), whereas PLP may have a different amino acid sequence (or may be post-translationally modified). Using specific PHI and VIP radioimmunoassays, the distribution of PLP was found to parallel that of VIP in rat and porcine brain, being highest in cerebral cortex, amygdala, and hippocampus. PLP, like VIP, is abundant in rat retina and can be included in the growing list of retinal peptides. This highly correlated distribution of VIP and PLP may be explained by the recent discovery that they are derived from the same precursor (Itoh, N., K. Obata, N. Yanaihara, and H. Okamoto (1983) Nature 304: 547-549).(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1983

Cholecystokinin peptides in the brain and pituitary of the bullfrog Rana catesbeiana: distribution and characterization.

The distribution of CCK peptides in the bullfrog brain was determined with a CCK radioimmunoassay. Frog brain CCK distribution resembles rat porcine and human brain in that CCK concentration is moderate to high in hypothalamus, diencephalon, and medulla (3 18.4 ng/mg protein) and low in cerebellum (0.6 ng/mg protein). However, unlike all mammalian species examined, the CCK content of frog cerebral cortex, hippocampus and olfactory lobe is quite low (0.03 0.23 ng/mg protein). The elution of CCK-like peptides in frog brain extracts was determined on two HPLC systems. On both systems the bulk of the CCK-like material eluted with CCK 8 sulfate and separated from gastrin and other CCK peptides. These data suggest that though the chemical structure of CCK appears to be the same in the brains of frogs and mammals, the distribution of CCK in the brain appears to have shifted during the course of evolution, becoming a cortical, hippocampal, and olfactory system peptide only in more evolved organisms.

Animals↗
PubMed1983

Rapid development of tolerance to the behavioural actions of cholecystokinin.

Cholecystokinin (CCK) acts acutely to inhibit food consumption in fasted rats, mice, sheep, pigs, monkeys and humans. CCK has been proposed as a satiety signal, inducing the behavioural sequence of satiety, or as an aversive internal stimulus, which inhibits food intake by inducing malaise. Reductions in food intake and related exploratory behaviours are initiated by CCK at its peripheral receptor in the gut, which appears to transmit sensory feedback via the vagus nerve to brain regions mediating appetitive behaviours. The therapeutic potential of CCK as an appetite suppressant in obesity syndromes rests on the demonstration of significant, long-lasting body weight reduction. Chronic CCK administration by repeated injections is problematic, since this peptide is rapidly degraded in vivo. We chose the Alzet constant infusion osmotic minipump to investigate possible alterations in body weight and food intake during continuous infusion of CCK. We now report that no change was detected in either body weight or total daily food consumption at any time point during 2 weeks of intraperitoneally (i.p.) infused CCK. The mechanism underlying the lack of chronic CCK effects appears to be a rapid development of behavioural tolerance. Acute challenge doses of CCK which induced satiety-related behaviours in saline-infused rats were ineffective in CCK-infused rats. The behavioural tolerance was apparent within a few hours of minipump implantation. These results provide the first evidence that rapid and reversible tolerance develops to the actions of a gut peptide.

Animals↗
PubMed1983

Effects of time and experience on hippocampal neurochemistry after damage to the CA3 subfield.

Bilateral injections of kainic acid into the hippocampal CA3 subfield destroyed the CA 3 pyramidal cells and produced a behavioral impairment, an inability to solve spatial maze problems. The behavior recovered, however, with daily experience in a maze task, and the rate of recovery was accelerated by additional daily experience. This recovery of function could be the result of compensatory changes in the distribution or function of the various hippocampal pathways. In the present experiment, this possibility was investigated neurochemically. Five putative neurotransmitters or their synthetic enzymes were measured in dissected regions of the hippocampal formation. Both the long-term effects of the lesions and the effects of behavioral training were determined. A number of alterations in hippocampal neurochemical systems were detected. Acute changes due to the lesions included a widespread loss of glutamate, and regionally specific decreases in glutamic acid decarboxylase (GAD) activity and cholecystokinin (CCK) and norepinephrine (NE) concentrations. Long-term changes included a decline in choline acetyltransferase (ChAT) activity throughout the hippocampal formation, and increases in NE in certain regions. Behavioral testing prevented the decline of ChAT activity, and increased the concentrations of GAD and CCK. The neurochemical conditions present at the time when trained rats recovered behavioral function may indicate the crucial conditions for the occurrence of the behavior.

Animals↗