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T Smock

Publications and source records attributed to T Smock.

32 records · Page 2Linked to original sources

Spontaneous and neurogenic constriction of microvasculature in the rat hippocampal slice.

The hippocampal slice is characterized by laminar organization and defined synaptic circuitry and provides an in vitro model system for the study of neuronal membrane properties, the action of putative neurotransmitters, and synaptic plasticity. Because the hippocampus is densely vascularized and hippocampal microvessels respond to a variety of stimuli that also affect the activity of neurons in the slice, the preparation is also especially well suited to investigating the physiologic relationship between neurons and intraparenchymal blood vessels. Here we address the issue of potential neurogenic control of cerebral microvasculature using electrical stimuli and specific neurotoxins. A small proportion of slice microvessels displayed spontaneous rhythmic activity that was independent of any exogenous stimulus. The majority of slices examined contained microvessels that responded to a train of electrical impulses delivered to discrete neural pathways. Under particular stimulus conditions, the vascular response could be completely blocked by 1 microM tetrodotoxin. The results are taken to support the existence of a neurogenic influence on penetrating arterioles.

Animals↗

Effects of ACTH(1-24) on single unit activity in the brainstem of the rat.

Central administration of corticotropin-like peptides generally blocks the analgesic action of opiate ligands, yet it is unclear whether this is due to an independent hyperalgesic action of corticotropin or to some other mechanism. Single cells in the ventromedial medulla of the anaesthetized rat were characterized as either excited by noxious stimuli or inhibited. Injections of ACTH(1-24) excited cells that were excited by noxious stimuli and inhibited cells that were inhibited by noxious stimuli. The results support an independent role for corticotropin-like peptides in pain-modulating mechanisms.

Animals↗

Action of pro-opiomelanocortin products on the rat vas deferens.

Behavioral study of pro-opiomelanocortin products indicates that beta-endorphin and corticotrophin-like peptides have antagonistic effects. However, these peptides have similar actions on the rat vas deferens. beta-endorphin, alpha-MSH and ACTH each inhibit electrically evoked contraction of the duct, but the corticotrophin derived peptides are tenfold more potent on a molar basis (ED50 = 9 nM). Pharmacological analysis shows that the action of corticotrophin-derived peptides does not involve an opiate receptor mechanism. The results are discussed in terms of the central action of the peptides.

Adrenocorticotropic Hormone↗

Neuropeptide routing in the bag cells: kinetic differences in the appearance of newly labeled peptides in transport and secretion.

The bag cell neurons of Aplysia synthesize and secrete several peptides. Some of these, in addition to the egg-laying hormone (ELH), are strongly implicated in the various alterations of central neuronal activity that accompany an electrical discharge of the bag cells. Thus, the secreted peptides appear to play a variety of roles in the animal's physiology. We have been interested in the intracellular mechanisms that precede peptide secretion from the bag cells because of the evidence that most, if not all, of these peptides are derived from a common precursor. Our objective has been to determine if presumed products of this precursor are processed coordinately following their synthesis. We have concentrated on two peptides (ELH and the acidic peptide, AP) because they are most easily identified in our analytical systems. On pulse-chase radiolabeling of the cells in vitro, we found that labeled AP appears before labeled ELH in axonal transport. This observation is not easily accounted for by the assumption, taken from studies of other peptide-secreting cells, that a precursor to both peptides is loaded into secretory granules before further processing ensues. Since the initial disproportion in the representation of the peptides in transport is no longer detectable at long chase times (18 and 24 hr), we examined the possibilities that ELH production is delayed relative to that of AP or that AP is degraded more rapidly than ELH. No evidence was found for either process. The disproportion between the newly labeled peptides in transport was evident on analysis of the medium bathing bag cells depolarized after 24 hr of chase.(ABSTRACT TRUNCATED AT 250 WORDS)

Axonal Transport↗

ACTH1-24 blocks opiate - induced analgesia in the rat.

Samples of 1 microliter containing 15 microgram of morphine sulfate with or without 1 microgram of synthetic ACTH were injected into the fourth ventricle of rats. The inclusion of ACTH eliminated the analgesic effect of morphine as evaluated by the tail-flick test, both in restrained and in unrestrained, lightly sedated animals. The same result was obtained when beta-endorphin was used to bring about analgesia. Since the effect of the peptides was shown to be mediated by central actions alone, the results are discussed in light of the brain ACTH/beta-endorphin system.

Adrenocorticotropic Hormone↗

Evidence for mediation of a neuronal interaction by a behaviorally active peptide.

Egg laying hormone, a peptide neurohormone with an approximate molecular weight of 6000, was isolated from the region of the abdominal ganglion of Aplysia that contains the neuroendocrine bag cells and purified by gel filtration chromatography, isoelectric focusing, and dialysis. A 1-min local application of egg laying hormone to the identified neuron R15 produced prolonged (greater than 1 hr) augmentation of impulse activity in this neuron. The distinctive quality and prolonged duration of the response are apparently identical to the previously described response to electrically elicited bag cell activity. The results provide evidence that egg laying hormone is the mediator of this prolonged neuronal interaction.

Animals↗

A cytochemical study of the bag cell organs of Aplysia californica.

Egg-laying hormone in Aplysia californica is synthesized and secreted by cells that seem to be homogeneous ultrastructurally and electrophysiologically. Several conventional methods have been used to demonstrate histochemical homogeneity and special staining techniques based on the known properties of the hormone show the neuroendocrine organ to be uniform in appearance. Furthermore, since stain specificity for egg-laying hormone is demonstrable using release and biochemical studies, the authors concluded that the organ consists of a population of biochemically homogeneous neurons.

Aplysia↗

Biochemical isolation and physiological identification of the egg-laying hormone in Aplysia californica.

It has been determined that the bag cells of Aplysia californica produce two polypeptide species that comigrate on electrophoretic gels containing sodium dodecyl sulfate. By this separation procedure both species can be assigned a molecular weight of approximately 6,000. One of these molecules has an Rf of 0.65 on alkaline discontinuous electrophoresis gels, an isoelectric point at pH 4.8, a gel filtration molecular weight of approximately 12,000, and has no known biological function. The other does not enter alkaline disk gels, has an isoelectric point at approximately pH 9.3, shows a gel filtration molecular weight consistent with that determined by SDS gel electrophoresis, and is the egg-laying hormone.

Animals↗

Precursor and product processing in the bag cell neurons of Aplysia californica.

Posttranslational processing in the biosynthesis of the egg-laying hormone (ELH) by the bag cell neurons of Aplysia californica was studied. The precursor (pro-ELH) to ELH was found to be resistant to solubilization in denaturant-free media throughout its lifetime. Its principle products show a similar insolubility for 3 h, but two of these, ca. 6,000 daltons, subsequently become readily recoverable in the low-speed supernatant of a homogenate of the cells. The remaining product shows no change in solubility characteristics. From studies employing ultracentrifugation and examination of axoplasmic transport, the solubility shift for the lower molecular weight products is interpreted to represent the liberation of secretory vesicles into the cytoplasm from larger membranous associations. This event is accompanied by, but does appear to be dependent upon, a 15% reduction in the molecular weight of one of the products. These findings are considered in the light of the extensively studied posttranslational processing regimen for the production of insulin in the pancreatic beta cell.

Animals↗

Peptidergic transmission in the brain. VI. Behavioral consequences of central activation.

Having described a peptidergic transmitter system in the rat brain, we now begin to evaluate its behavioral function. We stimulated cell bodies in the medial amygdaloid nucleus (AME) with indwelling bilateral electrodes. These cell bodies contain a vasopressin-like peptide and send fibers to the hippocampus where the peptide is released upon stimulation. There the peptide inhibits hippocampal output in the awake rat just as it does in the anesthetized rat and in the rat brain slice. The stimulation reorganizes behavior with the same latency and duration as the hippocampal effect. For about 15-20 minutes after the brief stimulus, rats remain motionless with eyes wide open. This "freezing" state is punctuated by episodes of exploratory behavior. The stimulus appears to have a positive affective quality. Review of the literature in light of the present results indicates a probable role for this peptidergic system in the generation of sexual behavior in male rats.

Amygdala↗

Peptidergic transmission in the brain. V. Systemic correlates of central activation.

Inhibition of the hippocampus by the medial amygdala is mediated by vasopressin-like peptide. Because vasopressin has action on the periphery as well as the brain, we conducted experiments to evaluate the relationship between possible peripheral actions and the central effects of the endogenous peptide. In the acutely anesthetized rat, peptide-mediated inhibition of the hippocampus is not associated with significant changes in heart rate, blood pressure or body temperature. Peripheral injections of peptide agonist fail to evoke the central inhibition, and peripheral injections of peptide antagonist fail to block the central inhibition. Stimulation of central nuclei that contain vasopressin or a similar peptide also fail to duplicate the effect of stimulating the amygdala. We conclude that the peptidergic transmission is independent of peripheral causes or correlates.

Amygdala↗

Peptidergic transmission in the brain. III. Hippocampal inhibition by the amygdala.

The mechanism of arginine vasopressin (AVP) action in the rat hippocampus has been determined. The peptide activates inhibitory interneurons and constricts cerebral microvessels. In the whole animal, each of these direct actions has secondary consequences for the excitability of pyramidal cells. Recent studies have shown that a peptide similar to AVP mediates endogenous neurotransmission in the hippocampus. Here we report experiments showing that the endogenous peptide activates the same mechanisms as exogenously applied AVP. The endogenous AVP-like peptide has no effect on the presynaptic fiber volley, or on pure somatic and dendritic postsynaptic potentials. These results are taken to exclude presynaptic mechanisms as explanations for the peptide's action. The endogenously released peptide inhibits individual pyramidal cells in single unit recording and excites presumed interneurons, just as AVP itself is known to act. The endogenous peptide is released only by stimuli applied to a nucleus that contains immunoreactive AVP and projects to the hippocampus.

Amygdala↗

Peptidergic transmission in the brain. IV. Sex hormone dependence in the vasopressin/oxytocin system.

The medial amygdaloid nucleus (AME) synthesizes a peptide similar to arginine vasopressin and projects peptidergic fibers to the ipsilateral hippocampus in the male rat. In previous studies, we have shown that the peptide acts as a transmitter and, using in vitro and in vivo electrophysiology, we have characterized its mechanism of action. Previous anatomical work has shown that the peptidergic fibers are more dense in male rats than females and are obliterated entirely by castration. Here we report the results of our attempt to find an electrophysiological correlate of these anatomical findings. First, we show specific mediation by a vasopressin- or oxytocin-like peptide by use of a structural vasotocin antagonist. Then we show that castration obliterates the peptidergic signal in males. However, we were unable to find any sex difference that corresponded to the male/female disparity noted in the density of the peptidergic fibers. The strength, nature and stimulus-response characteristics were the same between males and females. Apart from a very subtle difference in the duration of the signal, no physiological correlate of the sexual dimorphism could be found with our techniques. We conclude that the neurophysiology partly complements the anatomy and biochemistry of this system.

Amygdala↗