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A C Towle

Publications and source records attributed to A C Towle.

At least 37 records · Page 2Linked to original sources
PubMed1987

Cellular localization of tyrosine hydroxylase mRNA and its regulation in the rat adrenal medulla and brain by in situ hybridization with an oligodeoxyribonucleotide probe.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamines in neural tissues and adrenal medulla. To study the expression of the TH gene and its regulation in adult and developing neural tissues, we have synthesized an oligodeoxyribonucleotide probe (oligomer) that is specific for TH mRNA. Using Northern blot hybridization of polyadenylated RNAs from adrenal gland, brain stem, liver, and cerebral cortex with the 32P-labeled oligomer, a single TH mRNA of 1.9 kb was detected in adrenal gland and brain stem but not in liver and cerebral cortex. Using this TH-specific oligomer, TH mRNAs were localized to the chromaffin cells in the adrenal medulla and to catecholaminergic neurons in locus coeruleus and substantia nigra by in situ hybridization histochemistry. After reserpine administration, the intensity of hybridization signal was increased to threefold that of normal in sections of adrenal medulla and twofold that of normal in locus ceruleus. No difference in hybridization signal intensity was observed in the substantia nigra of normal and reserpine-treated animals. Use of this specific TH probe in in situ hybridization procedures represents a powerful approach to the study of regulation of TH gene expression at the cellular level.

Adrenal Medulla↗
PubMed1987

Significant relationship between renin suppression and atrial natriuretic peptide (alpha-hANP) during volume loading in hypertensive men.

We have studied eight men with moderate hypertension to determine the atrial natriuretic peptide (alpha-hANP) response to acute volume expansion. Rapid infusion of 1,000 ml 0.9% saline (10-20 min) caused an increase in central venous pressure (4.7 +/- 1.6 cmH2O) while blood pressure and pulse pressure (arterial baroreceptor load) did not change. Stroke volume and heart rate were not affected by the volume load but plasma renin activity (PRA) was significantly suppressed (from 0.83 +/- 0.14 to 0.68 +/- 0.34 microgram AI I/ml-h; p less than 0.01). A significant hemodilution was also observed. Renal sodium excretion was significantly increased. Arterial alpha-hANP increased significantly from 21.1 +/- 6.1 to 30.5 +/- 4.0 pmol/l (p less than 0.02) during volume expansion. There was a significant correlation between corrected plasma volume increase (urine volume subtracted from the infused volume) and alpha-hANP plasma elevation (r = 0.78; p less than 0.05). There was also a significant negative correlation between changes alpha-hANP and PRA (r = -0.78, p less than 0.05). We conclude that only moderate volume loading in human hypertensives is a mechanism for increase in plasma alpha-hANP levels. The significant negative correlation between changes in alpha-hANP and PRA suggests that alpha-hANP may be the humoral factor at least partly responsible for suppression of renin in hypertensive man. Since increased fluid volume also affects sympathetic renal efferents as well as vasopressin secretion, our observed relationship between volume load and renin may well be related also to such mechanisms.

Adult↗
PubMed1987

Effects of chronic salt loading on plasma atrial natriuretic peptide (ANP) in the spontaneously hypertensive rat.

Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was measured in spontaneously hypertensive rats (SHR) during chronic salt loading (1.5% NaCl in drinking water). During the 3-week experimental period mean arterial blood pressure, heart rate, urinary sodium excretion and body weight was assessed in salt-loaded as well as in control rats. The sodium excretion was more than 10-fold increased in the rats on the high salt diet. The plasma ANP concentration was significantly increased only 24 h after the start of the high salt intake. Thereafter plasma ANP concentrations were not significantly different from values obtained in control rats. The blood pressure was significantly increased after 3 weeks on the high salt diet. At the end of the 3-week experimental period the rats were subjected to a 10 and 20% acute volume expansion with homologous whole blood. During this intervention the increase in plasma ANP concentrations was blunted in the high salt rats compared to the control group. It is concluded that during chronic salt loading in SHR there is an initial rise in plasma ANP levels and that other hormonal and neuronal systems are more important in the long term maintenance of fluid and electrolyte balance.

Animals↗
PubMed1987

Identification of somatomedin/insulin-like growth factor immunoreactive cells in the human fetus.

Somatomedins/insulin-like growth factors (Sm/IGFs) are present in blood and in extracts from multiple tissues of the human fetus and induce the proliferation of cultured human fetal cells. To identify the cellular location of immunoreactive Sm/IGF in human fetal tissues, we have performed immunocytochemistry in tissues from prostaglandin-induced human fetal abortuses of 12 to 20 wk in gestation. Every tissue studied except the cerebral cortex contains Sm/IGF immunoreactive cells. Cells staining positively include hepatocytes, hepatic hemopoietic cells, columnar epithelia of the pulmonary airways, intestine and kidney tubules, adrenal cortical cells, dermal cells, skeletal and cardiac muscle fibers, and pancreatic islet and acinar cells. Immunostaining was specific for Sm/IGFs, but because of the cross-reactivity of the antibodies it was not possible to determine whether the immunoreactivity represented Sm-C/IGF I, IGF II, or both. Liver contained the greatest proportion of immunoreactive cells, while the thymus and spleen had only a few immunostained cells. With the possible exception of dermal and some adrenal cortical cells, the immunoreactive cells do not appear to be the primary sites of Sm/IGF synthesis, because parallel in situ hybridization histochemical studies using Sm/IGF oligodeoxyribonucleotide probes show that Sm/IGF mRNAs are localized predominantly to fibroblasts and mesenchymal cells. Therefore the immunoreactive cells identified in this study may define sites of action of Sm/IGFs.

Adrenal Glands↗
PubMed1987

Glutamate-positive neurons in the somatic sensory cortex of rats and monkeys.

The morphology and laminar distribution of neurons labeled with an antiserum prepared against glutamic acid (Glu) conjugated to keyhole limpet hemocyanin have been studied in the somatic sensory cortex of rats and monkeys. In both species, the vast majority of immunostained neurons are pyramidal; some nonpyramidal neurons are also present. Positive neurons are observed in all cortical layers, although variations are found in the percentage of Glu-positive neurons in the different layers. In rats they are most numerous in layer V (36%), followed by layer II (33%), layer III (32%), and layer VI (29%). In layer IV, 13% of all neurons are positive. Immunoreactive neurons are very sparse in layer I. In monkeys, Glu-positive neurons represent 51% of all neurons in layer V, 49% in layer III, 40% in layers II and VI, and 19% in layer IV. No differences are evident in the laminar distribution of Glu-positive neurons among cytoarchitectonic areas 3a, 3b, 1, and 2. As in rats, Glu-positive neurons are very sparse in layer I. Since Glu and GABA metabolisms are closely related, double-labeling experiments were performed in which thin, adjacent paraffin sections were stained alternately with the anti-Glu serum and with an anti-GABA serum. The 2 populations are almost completely segregated, even though a small fraction of neurons (less than 5%) are labeled by the antisera against both antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Brainstem localization of a thyrotropin-releasing hormone-induced change in respiratory function.

When rats received microinjections of 100 ng thyrotropin-releasing hormone (TRH) into the medial portions of the nucleus tractus solitarius and 12th nucleus or raphe obscurus, at the level of the obex, a significant decrease in the inspiratory time was found. Examination of TRH immunocytochemistry revealed a high density of TRH-positive nerve terminals in these regions, especially the more caudal aspects. If serotonin was depleted by neonatal 5,7-dihydroxytryptamine treatment, the respiratory response of the adults to TRH appeared potentiated. Even though the neonatal 5,7-dihydroxytryptamine reduces the occurrence of TRH-positive cell bodies, TRH-positive fibers were not appreciably altered. These results are discussed with regard to a possible role of endogenous TRH in the brainstem on rhythmic respiratory activity.

5,7-Dihydroxytryptamine↗
PubMed1986

Acute volume expansion as a physiological stimulus for the release of atrial natriuretic peptides in the rat.

The concentration of immunoreactive atrial natriuretic peptide(s) (ANP) was measured in normovolemic conscious rats and 15 min after 10% and 20% blood volume expansion. A 20% blood volume expansion caused a 2-fold increase in plasma ANP. While plasma ANP increased linearly, atrial levels of ANP remained unaltered. The increase in plasma ANP parallelled increases of central blood volume and central venous pressure. It is concluded that acute blood volume expansion is a major physiological stimulus for the release of atrial natriuretic peptides into the circulation.

Animals↗
PubMed1986

Early postnatal administration of 5,7-dihydroxytryptamine: effects on substance P and thyrotropin-releasing hormone neurons and terminals in rat brain.

Substance P, thyrotropin-releasing hormone (TRH) and serotonin are putative neurotransmitters which have been proposed to co-exist in some brain neurons. Our previous immunocytochemical and biochemical studies have demonstrated that 85-100% of all serotonin neurons are destroyed following neonatal 5,7-dihydroxtryptamine (5,7-DHT) treatment. In this study, we have determined the effect of neonatal 5,7-DHT and desipramine (DMI) treatment on the biochemical content and immunocytochemical localization of substance P and TRH throughout the brain. Interestingly, we have observed that virtually all substance P- and TRH-immunoreactive cells in the ventral pons-medulla are destroyed by the neurotoxin. However, peptide-containing neurons in other regions were not affected. Additionally, we measured the peptide content and found that TRH is significantly decreased in the spinal cord (-50%) and pons-medulla (-20%), but not in other brain regions. Substance P content was not significantly altered in any region, even after a greater than 90% reduction of serotonin. These data indicate that the co-localized substance P and TRH forms a small proportion of the total peptide in brain.

5,7-Dihydroxytryptamine↗
PubMed1986

Cellular localization of proglucagon/glucagon-like peptide I messenger RNAs in rat brain.

Techniques of in situ hybridization histochemistry, Northern blot hybridization, and immunocytochemistry were used to investigate the biosynthesis of glucagon-like immunoreactants (GLIs) in rat brain. Cells in the nucleus tractus solitarius of the medulla oblongata of adult rat brain hybridized to a synthetic oligonucleotide probe (GLP-I oligomer) corresponding to nucleotide sequences in pancreatic proglucagon mRNA encoding glucagon-like peptide I (GLP-I), and stained with antisera specific for two antigenic determinants of pancreatic proglucagon, glucagon, and GLP-I. These data suggest that there is de novo synthesis of proglucagon in cells of the nucleus tractus solitarius via expression of a proglucagon mRNA similar to that produced in pancreas. Previous studies have shown that cells in hypothalamus stain with GLP-I antisera, but not with glucagon antisera. However, cells in the hypothalamus did not hybridize with the GLP-I oligomer and may therefore produce a GLP-I immunoreactant that is encoded by a mRNA different from the pancreatic proglucagon-mRNA-encoding glucagon and GLP-I. Northern blot hybridizations with a cDNA probe encoding the entire pancreatic proglucagon sequence did not detect proglucagon/GLP-I mRNAs in polyadenylated RNAs (Poly A RNA) from adult rat brainstem and hypothalamus, probably because of their low abundance. Poly A RNAs from fetal rat brain, however, contained two mRNAs that hybridized to the proglucagon cDNA probe. One mRNA of 1,300 bases is the same size as pancreatic proglucagon mRNA. The second mRNA of 1,500 bases may encode the GLP-I immunoreactant detected in the hypothalamus of adult rat brain. The presence of neurons with glucagon and glucagon-like peptides in the nucleus tractus solitarius suggests a role of these peptides in gustatory and/or cardiopulmonary control.

Animals↗
PubMed1986

Prenatal ontogeny of the GABAergic system in the rat brain: an immunocytochemical study.

Prenatal development of the GABAergic system in the rat brain has been studied using an antiserum to GABA-glutaraldehyde-hemocyanin conjugates, specific for GABAergic neurons. The gamma-aminobutyric acid (GABA) system has been found to differentiate very early relative to other transmitter-identified neurons, such that by embryonic day 13 a well developed fiber network exists in the brainstem, mesencephalon and diencephalon, including a large projection in the posterior commissure and adjacent areas on the surface of the mesencephalon and tectum. Although no cell bodies are visible at this time, it appears that these fibers originate from the caudal brainstem and spinal cord. GABAergic cell bodies begin to appear on embryonic day 14 in the lateral cortical anlage. By embryonic day 16, they are also visible in the basal forebrain and in all regions of cortex where they are located in three zones: in layer I, below the cortical plate, and in the intermediate zone. Also contained in the outer part of layer I is a dense fiber plexus which stains intensely for GABA. These fibers may be part of the first contingent of cortical afferents to invade the telencephalic vesicle, an event which is thought to be a stimulus for the beginning of neuronal differentiation in this region. By E18, two bands of immunoreactivity are visible in layer I, which probably contain both cell bodies and fibers. The trajectories taken by growing GABAergic fibers in the brainstem, mesencephalon and diencephalon at embryonic day 13 and at subsequent stages of development are coincident with regions of both monoaminergic and peptidergic differentiation and appear to correspond to recently reported patterns of benzodiazepine receptors which appear slightly later. The early differentiation of the GABAergic system could indicate a trophic role for GABA in early brain development, possibly involving receptors for this neurotransmitter or related substances.

Animals↗
PubMed1986

Increased plasma levels of atrial natriuretic peptide in patients with congestive heart failure.

Atrial natriuretic peptide (ANP) is a recently discovered hormone, originating from atrial myocardium. The peptide (or family of peptides) induces potent diuretic/natriuretic, vasorelaxing and aldosterone inhibitory effects. We have investigated plasma concentrations of immunoreactive ANP in 10 patients with congestive heart failure (CHF). Mean plasma ANP concentrations were more than three times higher in CHF patients than in a matched control group. High plasma ANP concentrations in pathophysiological conditions with a high preload combined with salt and water retention is consistent with a physiological role of this hormone to correct hypervolemia by causing natriuresis and diuresis. It is concluded that ANP homeostasis is altered in patients with CHF and that this hormone may be of importance in the pathophysiology of CHF.

Atrial Natriuretic Factor↗
PubMed1986

Increase in plasma atrial natriuretic peptides during acute volume expansion in hypertensive man.

A new hormonal system originating from cardiac atria has recently been discovered. These peptide hormones have important functions in the regulation of blood volume and fluid homeostasis. We have measured plasma concentrations of atrial natriuretic peptides (ANP) in two patients during acute volume expansion. ANP concentrations increased in relation to an increase in right atrial pressure, and significant diuresis/natriuresis was observed. We conclude that hormonal as well as neuronal mechanisms are activated by acute volume loading in man.

Atenolol↗
PubMed1985

Bombesin-like immunoreactivity in the central nervous system of capsaicin-treated rats: a radioimmunoassay and immunohistochemical study.

The neuroanatomical distribution of bombesin-like immunoreactivity (BLI) in the rat central nervous system was investigated using radioimmunoassay and immunohistochemistry. Whereas cross-reactivity of the bombesin antiserum with substance P was problematic in the immunohistochemical experiments, no significant cross-reactivity with substance P was apparent in the radioimmunoassay. Results from the radioimmunoassay studies reveal particularly high concentrations of BLI in the hypothalamus, thalamus, medulla and spinal cord. Adult rats treated neonatally with capsaicin displayed significant depletions of somatostatin-like and substance P-like immunoreactivity and a small, statistically significant, reduction of BLI in the cervical spinal cord. Capsaicin treatment significantly reduced substance P-like immunoreactivity, but not somatostatin-like immunoreactivity, in the medulla and resulted in a small BLI depletion of borderline statistical significance in this brain region. Neonatally administered capsaicin treatment had no effect on the thalamic concentration of any of these three neuropeptides and neurotensin-like immunoreactivity was unchanged in all brain regions studied. These results suggest that the source of some of the BLI found in the spinal cord may be capsaicin-sensitive dorsal root ganglion cells.

Animals↗
PubMed1985

Altered respiratory response to substance P in capsaicin-treated rats.

The present investigation sought to examine the importance of substance P in the altered respiratory activity after neonatal capsaicin administration. Halothane-anesthetized adult rats given capsaicin neonatally exhibit a decreased basal minute ventilation with PaCO2 equal to and PaO2 greater than vehicle injected controls. In addition, the minute ventilation-PaCO2 curve was displaced to the right. Acute bilateral cervical vagotomy severely blunted the minute ventilation response to PaCO2 and abolished the differences in ventilation between capsaicin treated and control rats. Neonatal capsaicin significantly reduced pons-medulla substance P content but not TRH, serotonin or 5-hydroxyindole acetic acid. Immunohistochemical studies revealed that substance P fibers of the trigeminal spinal nucleus were the most severely affected in the brain stem and that substance P fibers in the lung were totally absent. The intracerebroventricular administration of substance P increased minute ventilation similarly in both control and capsaicin treated rats, largely as a result of increases in tidal volume. The minute ventilation-PaCO2 curve was similar in both groups after substance P administration. Simultaneous administration of the peptidase inhibitor captopril with substance P increased the respiratory response to substance P in normal rats. Administration of captopril to capsaicin treated rats restored the ventilation-PaCO2 curve to the position observed in normal rats. The hypotensive response to intracerebroventricular captopril alone in control rats was less profound in rats given neonatal capsaicin. These results are consistent with the thesis that respiratory depression after capsaicin treatment is at least in part due to the loss of substance P primary afferent nerve terminals in the brain stem, suggesting that substance P fibers in the brain stem may participate in the normal modulation of respiratory activity.

Animals↗
PubMed1985

Decreased serotonin content of embryonic raphe neurons following maternal administration of p-chlorophenylalanine: a quantitative immunocytochemical study.

Previous studies from this laboratory have suggested that serotonergic (5-HT) neurons may influence the differentiation of their embryonic target cells in the developing rat brain. The present study was designed to determine whether or not maternal p-chlorophenylalanine (pCPA) administration could deplete serotonin (5-HT) in developing 5-HT neurons during embryonic days 13-15, when the effects of pCPA on neuronal genesis have been observed previously. For this study, pCPA was administered to timed-pregnant rats and embryos were sacrificed at two different gestational ages, embryonic days 13-14 (E13-14) and 14-15 (E14-15). Immunotitration experiments were carried out on tissue sections, using an antiserum to 5-HT-hemocyanin conjugates to obtain a relative estimate of the amount of 5-HT contained within individual 5-HT neurons of embryos from pCPA-treated and control mothers. Diminished immunoreactivity as a consequence of addition of increasing amounts of antigen was then quantitated on a relative scale by comparison with the amount of immunoreactivity present when no antigen was added to the primary antiserum. Two major findings resulted from this study: maternal pCPA treatment depleted 5-HT by approximately 50% in developing 5-HT neurons at embryonic ages E13-14 and E14-15, but depletion appeared to be greatest in the youngest embryos; developing 5-HT neurons increased their content of neurotransmitter by approximately 10-fold during this one day of embryonic development, an effect which could be observed in both pCPA-treated and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The role of vagal afferents and carbon dioxide in the respiratory response to thyrotropin-releasing hormone.

Rats treated neonatally with pargyline and 5,7-dihydroxytryptamine to decrease central serotonin-containing neurons have an accentuated respiratory response to i.c.v. thyrotropin-releasing hormone (TRH). Since these treated rats also evidence an elevated PaCO2, we sought to evaluate the importance of CO2 in determining the magnitude of the respiratory response to TRH. Neonatal treatment with capsaicin or acute vagotomy also produced adult animals whose basal PaCO2 was elevated and whose respiratory response to TRH was greater than that seen in control rats with lower PaCO2 values. In normal rats, however, administration of CO2 immediately before and after TRH administration does not alter the subsequent response to TRH. Thus, it appears that TRH facilitates the processing of CO2-dependent afferent impulses, and that CO2 does not alter disposition or pharmacokinetics of TRH.

5,7-Dihydroxytryptamine↗