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J A Kessler

Publications and source records attributed to J A Kessler.

At least 127 records · Page 7Linked to original sources
PubMed1986

Isolated plasma membranes regulate neurotransmitter expression and facilitate effects of a soluble brain cholinergic factor.

The choice of which transmitter will be expressed by a neuron is influenced by diffusible differentiating factors produced by a variety of nonneuronal cells. In this study we show that human, bovine, and rat brains contain a soluble heparin-binding factor that stimulates cholinergic and peptidergic expression. We also show that neuronal contact with other cell membranes influences neurotransmitter development and acts synergistically with the effects of the soluble brain factor. Exposure of cultured sympathetic neurons to purified plasma membranes derived either from cultured Schwann cells or from cultured sympathetic neurons promoted expression of choline acetyltransferase (CAT), a cholinergic trait, and of substance P (SP). CAT activity and SP were also stimulated by a 50-kDa soluble protein that was purified 14,000-fold from human, calf, and rat brain by heparin-Sepharose affinity chromatography. CAT activity after concurrent treatment with plasma membranes and the soluble factor far exceeded the sum of the enzyme activities after the individual treatments, suggesting that membrane molecules and the factor facilitated each other. Thus, cell-surface molecules, which have been shown previously to influence neuronal morphogenesis and neurite elongation, may also help determine the transmitter phenotype of the neuron. Moreover, cell-surface molecules may modulate the effects of diffusible differentiating factors.

Animals↗
PubMed1985

Differential regulation of peptide and catecholamine characters in cultured sympathetic neurons.

Mechanisms regulating peptidergic, noradrenergic and cholinergic development were compared in dissociated cell cultures of neonatal rat sympathetic ganglia. The majority of cultured neurons contained at least two neurotransmitters and many neurons contained three or more. These studies were undertaken to determine whether co-existing transmitters were co-ordinately regulated by the environment. Co-culture of sympathetic neurons with ganglion non-neuronal cells increased substance P and choline acetyltransferase activity but decreased somatostatin and tyrosine hydroxylase activity. Conversely, elimination of non-neuronal cells virtually abolished neuronal expression of substance P and choline acetyltransferase and increased somatostatin and tyrosine hydroxylase. Consequently, under these conditions, somatostatin and tyrosine hydroxylase were similarly regulated, whereas substance P was associated with choline acetyltransferase. By contrast, stimulation of adenylate cyclase or treatment with membrane-permeable adenosine 3',5'-phosphate analogs increased tyrosine hydroxylase and decreased choline acetyltransferase, but had no effect on substance P or somatostatin levels. Moreover, potassium- or veratridine-induced membrane depolarization increased tyrosine hydroxylase but decreased substance P, somatostatin and norepinephrine levels. However, inhibition of neurotransmitter release with magnesium or calcium-free medium prevented the decrease in norepinephrine levels but not the decrease in substance P and somatostatin. Consequently, the effects of membrane depolarization on peptide levels cannot be ascribed to release and subsequent depletion of substance P and somatostatin and must result from decreased net synthesis (synthesis minus catabolism) of the transmitters. Nerve growth-factor treatment also differentially regulated transmitter metabolism; nerve growth factor increased protein-specific activities of tyrosine hydroxylase and choline acetyltransferase but did not increase the protein-specific content of substance P and somatostatin. Quantitative transmitter expression was also influenced by neuron density; increasing density elevated substance P and choline acetyltransferase activity but decreased somatostatin and tyrosine hydroxylase activity per neuron. Finally, culture of sympathetic neurons in a defined (serum-free) medium also altered some but not all traits, decreasing substance P, somatostatin and choline acetyltransferase without any change in tyrosine hydroxylase.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Parasympathetic, sympathetic, and sensory interactions in the iris: nerve growth factor regulates cholinergic ciliary ganglion innervation in vivo.

Interactions between peptidergic sensory nerves, noradrenergic sympathetic nerves, and cholinergic parasympathetic fibers were examined in the rat iris. The putative peptide neurotransmitter, substance P (SP), was used as an index of the trigeminal sensory innervation, tyrosine hydroxylase (TH) activity served to monitor the sympathetic fibers, and choline acetyltransferase (CAT) activity was used as an index of the parasympathetic innervation. Destruction of the sympathetic innervation by neonatal administration of 6-hydroxydopamine resulted in increased SP development and a smaller increase in CAT activity in the iris. Moreover, trigeminal ablation resulted in an increase in both TH and CAT activities. Finally, ciliary ganglionectomy resulted in increased SP and a smaller increase in TH activity in the iris. Administration of nerve growth factor (NGF) into the anterior chamber substantially increased both SP and TH activity in the iris and also increased CAT activity to a lesser extent. Moreover, administration of anti-NGF into the anterior chamber prevented both the sympathectomy-induced increases in SP and CAT, and the increases in TH and CAT activities after trigeminal ablation, suggesting that NGF mediated these increases. These observations suggest that the sympathetic, sensory, and parasympathetic innervations of the iris interact by altering availability of NGF elaborated by the iris. Regulation of iris CAT activity was examined in greater detail. Injection of the cholinergic toxin, AF64A, into the anterior chamber concurrently with ablation of the sympathetic and sensory innervations paradoxically increased CAT activity, whereas AF64A alone decreased CAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Environmental co-regulation of substance P, somatostatin and neurotransmitter synthesizing enzymes in cultured sympathetic neurons.

Mechanisms regulating peptide neurotransmitter metabolism were examined in dissociated cell cultures of the neonatal rat superior cervical ganglion (SCG). The pineal gland, a target of the SCG, produced a soluble factor (PCM) which increased substance P (SP) levels more than 15-fold in sympathetic neurons cultured in the presence of ganglion non-neuronal cells. Elimination of the non-neuronal cells decreased SP to negligible levels and abolished the stimulatory effects of PCM on SP expression. These observations suggest that ganglion non-neuronal cells stimulate sympathetic expression of SP, and that the pineal influences neuronal SP by acting on, or in concert with, ganglion support cells. PCM also influenced other neurotransmitter systems. In the presence of ganglion non-neuronal cells, PCM treatment increased choline acetyltransferase (CHAC) and decreased tyrosine hydroxylase (TOH) and somatostatin (SO). By contrast, PCM treatment of pure neuronal cultures resulted in negligible CHAC and SP levels and a doubling of SO with a small increase in TOH. In sympathetic neurons, SP expression may be associated with cholinergic development, whereas SO may be associated with noradrenergic phenotypic expression. Moreover, there is a reciprocal relationship between SP and SS expression by sympathetic neurons analogous to the previously described relationship between noradrenergic and cholinergic expression.

Animals↗
PubMed1984

Simultaneous expression of the SP-peptidergic and noradrenergic phenotypes in rat sympathetic neurons.

We previously observed that substance P (SP) levels in the rat superior cervical ganglion (SCG) rise sharply when the ganglion is maintained in vitro. To define the cellular localization of SP, sections of cultured SCG were stained for the possible dual presence of SP and tyrosine hydroxylase (TOH). Immunoreactivity to both SP and TOH was present in the majority of principal neurons. This observation suggests that principal sympathetic neurons can express simultaneously both the noradrenergic and SP-peptidergic phenotypes.

Animals↗
PubMed1984

Target organ regulation of substance P in sympathetic neurons in culture.

Target organ regulation of the putative, peptide neurotransmitter, substance P (SP) was examined in explants and dissociated cell cultures of the neonatal rat sympathetic superior cervical ganglion (SCG). SP levels increased dramatically in explants, rising more than 30-fold after 72 hr in culture. By contrast, peptide levels did not increase in dissociated ganglion cultures. However, SP increased almost 10-fold in cell cultures grown on a monolayer of cells derived from the pineal or salivary gland, targets of the SCG. By contrast, SP content did not increase in cultures grown on a substrate of cells derived from heart or intestine. Peptide identity in the SCG-target cocultures was authenticated by means of combined high-pressure liquid chromatography (HPLC)-radioimmunoassay. Moreover, immunohistochemical examination localized the peptide virtually exclusively to sympathetic neurons and nerve processes. Mechanisms mediating the sympathetic-target interaction were examined in SCG-pineal cocultures. The increase in peptide required interactions with living tissue, since substrates of killed target cells did not elevate SP levels. The target influences were not mediated by nerve growth factor or indoleamines, potential secretory products of pineal in culture. Veratridine treatment prevented the increase in SP in the cocultures, and tetrodotoxin blocked the veratridine effect, suggesting that sodium influx and membrane depolarization prevent SP elevation. Our observations suggest that sympathetic neuron interactions with target organs influence peptidergic expression, and that this interaction may be restricted to certain appropriate target structures.

Animals↗
PubMed1984

Non-neuronal cell conditioned medium stimulates peptidergic expression in sympathetic and sensory neurons in vitro.

Regulation of peptide neurotransmitter metabolism was examined in dissociated cell cultures of neonatal rat sympathetic and sensory ganglia. Previous studies have shown that pineal gland conditioned medium (PCM) influences substance P (SP) and somatostatin (SS) metabolism in sympathetic neurons in vitro. The present study examines mechanisms mediating these effects, and compares the actions of PCM on sympathetic and sensory neurons. PCM treatment increased SP levels in a dose-dependent manner without altering SS content of sympathetic neurons cultured in the presence of ganglion non-neuronal cells. Conversely, treatment of pure sympathetic neuron cultures resulted in a dose-dependent increase in SS, while SP was virtually undetectable at all doses. By contrast, dorsal root ganglion, trigeminal ganglion, and nondose ganglion sensory neurons contained SP both in the presence and absence of ganglion non-neuronal cells. Moreover, in each of these neuronal populations treatment with PCM increased SP levels both in the presence and in the absence of ganglion non-neuronal cells. These observations suggest that ganglion non-neuronal cells are necessary for sympathetic but not sensory neuron expression of SP. Moreover, PCM apparently stimulates SP in neurons which already contain the peptide, but the factor cannot foster de novo expression of the phenotype. PCM also influenced other transmitter traits in sympathetic neurons, suggesting linkage between mechanisms regulating peptides and other transmitters. In cultures containing both sympathetic neurons and non-neuronal cells, PCM treatment increased cholineacetyltransferase (CHAC) activity as well as SP, and decreased tyrosine hydroxylase (TOH) activity. By contrast, PCM treatment of pure sympathetic neuron cultures led to parallel increases in SS and TOH activity with negligible levels of SP and CHAC. These observations suggest that in sympathetic neurons, SS may be linked with noradrenergic expression, while SP is associated with cholinergic development, although more data are required to confirm this relationship. Moreover, there may be a reciprocal relationship between SP and SS expression by sympathetic neurons analogous to previous observations regarding cholinergic-noradrenergic expression (P. H. Patterson and L. L. Y. Chun, Proc. Natl. Acad. Sci. USA 71, 3607-3610, 1974; Dev. Biol. 56, 263-280, 1977). Consequently, neurotransmitter phenotypic expression is a complex process in which the environment regulates a balance among multiple transmitters.

Animals↗
PubMed1984

Development and regulation of substance P in sensory neurons in vitro.

Substance P (SP), the putative neuropeptide mediator of pain sensation, is contained in small dorsomedial sensory neurons of the dorsal root ganglion. Using different culture techniques and a sensitive radioimmunoassay for SP, we studied the ontogeny and regulation of this functionally important neurotransmitter in these neurons, obtained from neonatal rats. In ganglion explants grown by two different techniques, SP increased two- to threefold during the first week in culture. This rise was predominantly due to mechanisms intrinsic to the ganglion since it occurred in a fully defined medium, in the absence of added nerve growth factor (NGF). Blockade of protein synthesis with cycloheximide prevented the increase in SP suggesting that ongoing protein synthesis was necessary. Furthermore, depolarization with veratridine blocked the increase in SP, an effect which was reversed by tetrodotoxin, suggesting that transmitter characteristics in sensory neurons may be regulated by depolarization and/or transmembrane sodium flux. After a week in culture on a collagen substratum, supplementary NGF was necessary for the continued rise in SP. However, raising the dose of the trophic factor had no incremental effect on SP content, suggesting that NGF was acting primarily on neuronal survival. To approach such questions at the cellular level, ganglia were dissociated and grown in cell culture. In all cultures, SP increased 1.5-fold during the first day. In the absence of NGF, however, SP and cell numbers fell progressively after the second day. NGF elicited parallel increases in cell survival and SP content, supporting the suggestion that NGF acts primarily through neuronal survival to increase SP. Veratridine blocked the increase in SP in a tetrodotoxin-reversible manner, without affecting neuronal survival, indicating that the effects of these agents do not depend on normal ganglionic cellular architecture. Consequently, depolarization probably affects ganglionic sensory neurons directly. Our studies suggest that the development of transmitter characteristics in primary sensory neurons may be regulated by multiple factors, including neuronal activity as well as trophic agents such as NGF.

Animals↗
PubMed1984

Determination of synaptic phenotype: insulin and cAMP independently initiate development of electrotonic coupling between cultured sympathetic neurons.

Electrotonic coupling between pairs of sympathetic neurons dissociated from superior cervical ganglia of neonatal rats is rare when cells are cultured for 2 weeks in a nutrient medium plus serum and is common when cells are cultured for the same period in serum-free defined medium. This defined medium is the same nutrient medium with five added factors (progesterone, transferrin, putrescine, insulin, and selenium). When added singly to serum-containing medium, insulin and, to a lesser extent, selenium promote the development of electrotonic and dye coupling. The insulin effect is obtained with doses as low as 0.01 microgram/ml and is maximal after exposures from 3 to 5 days. The incidence of electrotonic coupling is also enhanced by exposure of cells to dibutyryl cAMP. This effect is obtained with doses as low as 0.1 mM, is faster (being maximal at approximately equal to 12 hr exposure), and is prolonged in the presence of the phosphodiesterase inhibitor caffeine. Butyrate itself promotes coupling to a small extent, but cAMP involvement is confirmed by similar effects of other membrane permeant analogues. Endogenous levels of cAMP are significantly elevated in cultures grown in the defined medium but not in those in serum-containing medium to which insulin or selenium are added. We conclude that the promotion of coupling by cAMP and by insulin or selenium are independent. The development of coupling in the defined medium thus seems to be a consequence of the addition of promoting substances (insulin, selenium) and the removal of an inhibitory effect of serum on cAMP levels.

Animals↗
PubMed1983

Substance P and somatostatin regulate sympathetic noradrenergic function.

Peptidergic-noradrenergic interactions were examined in explants of rat sympathetic superior cervical ganglia and in cultures of dissociated cells. The putative peptide transmitters substance P and somatostatin each increased the activity of the catecholamine-synthesizing enzyme tyrosine hydroxylase after 1 week of exposure in culture. Maximal increases occurred at 10(-7) molar for each peptide, and either increasing or decreasing the concentration reduced the effects. Similar increases in tyrosine hydroxylase were produced by a metabolically stable agonist of substance P, while a substance P antagonist prevented the effects of the agonist. The data suggest that the increased tyrosine hydroxylase activity was mediated by peptide interaction with specific substance P receptors and that peptides may modulate sympathetic catecholaminergic function.

Animals↗
PubMed1983

Appearance of enkephalin-immunoreactivity in rat adrenal medulla following treatment with nicotinic antagonists or reserpine.

Various neuroendocrine factors known to be important in the regulation of adrenal catecholamine biosynthesis were investigated for possible effects on enkephalin-like immunoreactivity (Enk-IR) in the adrenal medulla of the rat. In normal rats, the adrenal chromaffin cells were not stained for either methionine (met-) or leucine (leu-) Enk-IR. Staining for Enk-IR appeared in many chromaffin cells following denervation of the adrenal or treatment of rats with the nicotinic receptor antagonists chlorisondamine or pempidine. These observations suggest that splanchnic nerve activity normally depresses the levels of enkephalin-like peptides in chromaffin cells through a trans-synaptic mechanism involving acetylcholine release and nicotinic receptor stimulation. Paradoxically, treatment with reserpine also increased Enk-IR in chromaffin cells. However, this increase did not appear to result from the well known effect of reserpine to increase presynaptic nerve firing and tyrosine hydroxylase (TOH) activity, since no increase in Enk-IR was observed following treatment with phenoxybenzamine or 6-hydroxydopamine, drugs which also increase TOH activity through trans-synaptic mechanisms. The reserpine effect also did not appear to be mediated by a stress-induced increase in glucocorticoid hormones since glucocorticoid therapy alone did not increase adrenal Enk-IR. It is suggested that the increase in adrenal Enk-IR following reserpine may result from a direct action of reserpine on chromaffin cells.

Adrenal Medulla↗
PubMed1983

Substance P and somatostatin metabolism in sympathetic and special sensory ganglia in vitro.

Mechanisms regulating the content of the putative peptide transmitters, substance P and somatostatin, were examined in several neuronal populations in culture. Substance P levels increased more than 25-fold within 48 h in sympathetic neurons in the explanted rat superior cervical ganglion, and remained elevated for 4 weeks. Identity of the peptide was authenticated by combined high pressure liquid chromatography-radioimmunoassay. Veratridine prevented the increase of substance P in vitro, and tetrodotoxin blocked the veratridine effect, suggesting that sodium ion influx and membrane depolarization prevent peptide elevation. Veratridine (or potassium)-induced membrane depolarization released substance P into the culture medium through a calcium-dependent process. Consequently, at least some veratridine effects are attributable to release and subsequent depletion of ganglion peptide. However, the inhibitory effects of veratridine were far greater than could be accounted for by the quantity of peptide released, suggesting a separate influence on net synthesis (synthesis less catabolism) of substance P. Viewed in conjunction with previous in vivo studies, our observations suggest that trans-synaptic impulses, through the mediation of postsynaptic sodium flux, release substance P from sympathetic neurons and also regulate intracellular peptide metabolism. To determine whether the processes regulating substance P in sympathetic neurons reflect generalized mechanisms, a different peptide, somatostatin, was examined in sympathetic neurons; moreover, substance P was examined in a different neuronal population, special sensory neurons in the nodose ganglion. Substance P levels increased significantly in both sympathetic and sensory neurons after explantation, and somatostatin levels increased in sympathetic neurons. In each instance, the increase was dependent upon the presence of the calcium ions. Moreover, these increases were all prevented by veratridine, in a tetrodotoxin-sensitive manner. Our observations suggest that common regulatory mechanisms govern peptide transmitter metabolism in diverse neuronal populations.

Animals↗
PubMed1983

Interactions between the sympathetic and sensory innervation of the iris.

The interaction between peptidergic, sensory nerves and sympathetic fibers was examined in the rat iris. The putative peptide neurotransmitter, substance P, was used as an index of the sensory innervation, because the peptide is exclusively localized in the iris to trigeminal sensory fibers. Extirpation of the sympathetic, superior cervical ganglion resulted in an increase in iris content of substance P-like immunoreactivity (henceforth SP), suggesting that sympathetic terminals influence the peptidergic sensory innervation of the iris. The increase in iris peptide after sympathetic ganglionectomy was reversed by implantation of sympathetic ganglia into the anterior chamber of the eye. Pharmacological stimulation or blockade of sympathetic nerve impulse activity and pharmacological blockade of sympathetic axonal transport did not alter iris peptide, suggesting that these procedures did not mediate the sympathetic-sensory interaction. However, injection of nerve growth factor (NGF) systemically or into the anterior chamber increased iris peptide, reproducing the effects of ganglionectomy. Conversely, injection of antiserum to NGF (anti-NGF) into the anterior chamber decreased iris SP suggesting that endogenous trophic protein normally regulates sensory peptide. The effects of anti-NGF were transitory; iris peptide returned to normal after cessation of treatment. Consequently, anti-NGF administration apparently did not lead to sensory neuron destruction, but rather altered either the number of sensory fibers in the iris or the amount of peptide per fiber. Finally, injection of anti-NGF into the anterior chamber reversed the effects of sympathetic ganglionectomy, suggesting that NGF may mediate the sympathetic-sensory interaction. Our observations suggest that competition for target NGF may result in reciprocal regulation of the iris sympathetic and sensory innervation.

Adrenergic Fibers↗
PubMed1982

Regulation of substance P in adult rat sympathetic ganglia.

Factors regulating the putative peptide neurotransmitter, substance P, were examined in the adult rat sympathetic superior cervical ganglion (SCG). Surgical section of the preganglionic nerves resulted in a 55% increase in ganglion content of SP-like immunoreactivity (subsequently termed SP). Treatment with chlorisondamine, which blocks nicotinic ganglionic transmission, also increased SP, reproducing the effects of decentralization. Conversely, treatment with phenoxybenzamine, which reflexly increases sympathetic activity, reduced ganglion SP. Axotomy of the postganglionic nerves did not alter ganglion SP. Finally, treatment of rats as neonates with 6-hydroxydopamine, which selectively destroys principal ganglion neurons, profoundly decreased SP in the adult SCG. Our observations suggest that impulse activity of preganglionic nerves decreases ganglion SP in principal ganglion neurons through a transsynaptic process. Viewed in conjunction with previous work, our studies suggest that transsynaptic stimulation has opposite effects on SP and noradrenergic transmitter characters in the SCG.

Animals↗
PubMed1982

Antiserum to a new neuronal growth factor: effects on neurite outgrowth.

A new neuronal growth factor (CMF) isolated from mouse heart-cell-conditioned medium stimulates morphologic and biochemical development of mouse embryo sympathetic neurons [Coughlin et al, 1981]. Further analysis of CMF by chromatographic and electrophoretic procedures has shown that under nondissociating conditions, CMF activity is associated with very high molecular weight material. All biological activity eluted within the included volume of a Sepharose CL-2B column in a molecular weight range corresponding to approximately 5 X 10(6) daltons. Similarly, electrophoresis showed no activity and very little protein entering 3% polyacrylamide gels, whereas both protein and activity migrated through 0.6% agarose-1.2% acrylamide composite gels. To further characterize the biological effects of CMF on normal neuronal development, antibodies to CMF were employed. Rabbits immunized against CMF developed high titres of antibodies with activity specifically directed against CMF (anti-CMF). Although anti-CMF inhibited nerve growth factor (NGF)-stimulated neurite outgrowth from the neonatal superior cervical ganglion, it did not inhibit the NGF-stimulated increase in tyrosine hydroxylase activity. Moreover, ganglia incubated for 3 days in the presence of anti-CMF were subsequently capable of producing neurites when washed and cultured in medium free of antiserum. Thus, anti-CMF specifically blocked neurite extension without causing cell death or irreversible damage in ganglionic explants. Our observations suggest, therefore, that CMF or antigenically similar material is a requirement for neurite extension.

Animals↗
PubMed1981

Substance P in principal sympathetic neurons: regulation by impulse activity.

Regulation of the putative peptide neurotransmitter substance P was examined in the superior cervical sympathetic ganglion of the neonatal rat. Surgical decentralization (denervation) of the superior cervical ganglion increased ganglion substance P content. In cultured ganglia, the amount of substance P increased more than 50-fold after 48 hours, and this rise was dependent on protein and RNA synthesis. Veratridine prevented the increase in substance P in vitro, and tetrodotoxin blocked the veratridine effect; this suggests that sodium influx and membrane depolarization prevent substance P elevation. Immunohistochemical analysis of cultured ganglia indicated that substance P was present in the perikarya of principal sympathetic neurons and in ganglionic nerve processes. Transsynaptic impulses, through the mediation of postsynaptic sodium influx, may decrease substance P in sympathetic neurons.

Ganglia, Sympathetic↗
PubMed1981

Nerve growth factor stimulates development of substance P in the embryonic spinal cord.

Development of the putative neurotransmitter, substance P (SP), in the embryonic rat dorsal root ganglion (DRG) and spinal cord was defined in vivo. SP was not detectable by radioimmunoassay before day 17 of gestation (E17). On E17, cervical sensory ganglia contained 4 pg SP/ganglion, rising to 49 pg/ganglion at birth. The dorsal cervical spinal cord contained 0.75 ng SP/mg protein on E17, rising to 6 ng SP/mg protein on postnatal day 3. The ventral spinal cord contained approximately 20% of the SP content in the dorsal cord at each gestational age. Intrauterine forelimb amputation partially prevented the normal development increase of SP in sensory ganglia destined to innervate that limb, suggesting that target structures regulate the development of peptidergic neruons. Conversely, treatment with nerve growth factor (NGF) stimulated development of SP in the DRG. Moreover, NGF treatment increased SP in the dorsal spinal cord, suggesting that NGF can modulate development within the CNS, as well as peripheral structures. It is likely that the CNS effect reflects NGF peptidergic neruons. Conversely, treatment with nerve growth factor (NGF) stimulated development of SP in the DRG. Moreover, NGF treatment increased SP in the dorsal spinal cord, suggesting that NGF can modulate development within the CNS, as well as peripheral structures. It is likely that the CNS effect reflects NGF peptidergic neruons. Conversely, treatment with nerve growth factor (NGF) stimulated development of SP in the DRG. Moreover, NGF treatment increased SP in the dorsal spinal cord, suggesting that NGF can modulate development within the CNS, as well as peripheral structures. It is likely that the CNS effect reflects NGF action on peripheral ganglia, but a direct effect on the spinal cord has not been excluded. However, treatment with antiserum to NGF failed to significantly inhibit development of ganglion SP. The system of SP-containing neurons in the DRG may provide a convenient model for defining events regulating peptidergic maturation.

Animals↗