Nerve-mediated action of forskolin on guinea pig ileal mucosa

The effects of forskolin on myenteric neuronal activity and mucosal function were examined in guinea pig ileum. Forskolin increased the excitability of myenteric neurons, and increased mucosal chloride secretion by stimulating enteric neurons as well as by acting directly on enterocytes.     

Effects of methylene blue on electrical behavior of myenteric neurons

Summary Intracellular recording methods were used to investigate the action of methylene blue on electrical behavior of myenteric neurons in guinea pig small intestine. The neurophysiological studies were done in parallel with studies on contractile activity of the intestinal musculature. Methylene blue depolarized the membranes, increased the input resistance, augmented excitability and reduced postspike hyperpolarizing potentials in AH/Type 2 myenteric neurons. These effects, with the exception of suppression of postspike hyperpolarization, were reversed by exposure to elevated calcium. The mechanism of action of methylene blue appeared to be suppression of calcium-dependent potassium conductance in the neuronal membranes. The neuronal action of methylene blue was manifest as a release of excitatory neurontransmitter substances with evoked contraction of the small intestinal longitudinal muscle.     

Effects of methylene blue on electrical behavior of myenteric neurons

Intracellular recording methods were used to investigate the action of methylene blue on electrical behavior of myenteric neurons in guinea pig small intestine. The neurophysiological studies were done in parallel with studies on contractile activity of the intestinal musculature. Methylene blue depolarized the membranes, increased the input resistance, augmented excitability and reduced postspike hyperpolarizing potentials in AH/Type 2 myenteric neurons. These effects, with the exception of suppression of postspike hyperpolarization, were reversed by exposure to elevated calcium. The mechanism of action of methylene blue appeared to be suppression of calcium-dependent potassium conductance in the neuronal membranes. The neuronal action of methylene blue was manifest as a release of excitatory neurontransmitter substances which evoked contraction of the small intestinal longitudinal muscle.     

The enteric neural receptor for 5-hydroxytryptamine

An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using 3H-5-HT as a radioligand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of 3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these 3H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of 3H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of 3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of 3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.     

The enteric neural receptor for 5-hydroxytryptamine

Summary An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using³H-5-HT as a radiologand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of³H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these³H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of³H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of³H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of³H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.     

The response of cyclic 3′,5′-AMP and cyclic 3′,5′-GMP phosphodiesterases to experimental diabetes

Summary Alloxan diabetes caused a decrease in cyclic AMP phosphodiesterase in all affected rat tissues. Cyclic GMP phosphodiesterase activity was, however, decreased in adipose and liver, but increased in heart and uterus.This research was supported by U.S. Public Health Service grant RO1-AM19364-O1 and MARC training grant No. 1-TO2-GMO50000.     

Neuropeptide Y in the guinea-pig biliary tract

High concentrations of neuropeptide Y (NPY) have been demonstrated in the gall bladder (16.7 +/- 5.4 pmol/g), cystic duct (25.4 +/- 9.2 pmol/g) and common bile duct (54.7 +/- 11.5 pmol/g) of the guinea-pig using a recently developed radioimmunoassay. Immunoreactive NPY containing nerves were demonstrated in all layers of the biliary tree using immunocytochemistry, being particularly dense in the myenteric and mucosal plexuses.     

Increase in neuronal nitric oxide synthase content of the gastroduodenal tract of diabetic rats

This study examined the changes occurring in the pattern of distribution and expression of neuronal nitric oxide synthase (nNOS)-positive nerves in the gastroduodenal tract of streptozotocin-induced diabetic rats. The ganglion cells of the myenteric plexus of the gastric antrum of normal rats contain nNOS. We also observed nNOS-positive neurons and fibres in the myenteric plexus of the duodenum of normal rats. After the onset of diabetes, the number and intensity of staining of nNOS-positive nerve profiles in the gastric antrum and duodenum did not change significantly. However, Western blotting showed a significant increase in the expression of nNOS after the onset of diabetes. In conclusion, diabetes of 4 and 32 weeks duration induced an increase in the tissue content of nNOS in the gastroduodenum of rat. The increase in the level of nNOS in the gastroduodenum of diabetic rats may explain why impaired gastric emptying is common in patients with diabetes.     

Photoreceptor properties of an ectopic eye in the fleshfly,Sarcophaga bullata

Summary Ectopic eyes were produced on the fleshfly,Sarcophaga bullata by transplantation of imaginal eye discs. Electrophysiological and histological observations of these supernumerary eyes indicate the absence of synaptic connections between retinular cells and higher order neurons.Supported by an University of New Brunswick research grant to P.S. and NSF grant BNS-76-11921 and NIH grant 1-R01-EY-02487-01A1 to W.S.S.We would like to thank Dr I.A. Meinertzhagen for suggestions and Mary Johnson for technical assistance.     

Preferential neurotoxicity of pentobarbital on nerve and glial cells in culture

Summary The effect of pentobarbital was studied in a mixed population of nerve and glial cells dissociated from brains of 7-day chick embryos and maintained in culture. Pentobarbital-Na was added in various concentrations ranging from 5×10^–5 M to 1×10^–3 M. The neuronal density was monitored by counting of neurons, neuronal identity was established by staining for Nissl Bodies and acetylcholinesterase. Over a culture period of 3 weeks, it was found that the barbiturate exerts a preferential dose-dependent cytotoxic effect on neurons.The expert technical assistance of Miss A. Wolf is appreciated. This work was supported by grant 6-74-27, INSERM (Physiologie et Pathologie du Développement Nerveux).     

Adrenergic neuroplasticity is maintained in the nutritional rehabilitated adult rat

Summary This work examined the capacity of intact catecholaminergic axons to grow, in response to lesions, in the brain of adult rats following nutritional rehabilitation. The partially deafferented epithalamic habenula was used as a model to study neuronal plasticity. Noradrenergic neurons appear to maintain their plasticity in rats recovered from their postnatal undernutrition.Supported by a BRSG-UTMSH grant.Supported by a NIH grant.Acknowledgments. Thanks are due to Mrs Malka Gottesfeld for her invaluable assistance.     

Neuropeptide Y in the guinea-pig biliary tract

Summary High concentrations of neuropeptide Y (NPY) have been demonstrated in the gall bladder (16.7±5.4 pmol/g), cystic duct (25.4±9.2 pmol/g) and common bile duct (54.7±11.5 pmol/g) of the guinea-pig using a recently developed radio-immunoassay. Immunoreactive NPY containing nerves were demonstrated in all layers of the biliary tree using immunocytochemistry, being particularly dense in the myenteric and mucosal plexuses.Acknowledgments. JMA is a recipient of a Wellcome Trust Training Fellowship. JG is a visiting scholar from the Department of Pathology, Peking Medical College, Peking, China.     

Histochemical localization of glutamic acid dehydrogenase activity in the cuneate nucleus of the cat1

Summary Glutamic acid dehydrogenase activity was observed both in the neuropil as well as in several classes of cuneate neurons in the cat.The excellent technical assistance of Mr. C. T. Lee of our Histology Laboratory, and the support and encouragement of Professor W. C. Wong, Anatomy Department, are gratefully acknowledged.     

Nuclear localization of aldosterone in rat brain cells assessed by autoradiography

Summary Autoradiographic studies with³H aldosterone demonstrate nuclear concentration of hormone in neurons of the hippocampus, septum, allocortical regionss and brain stem reticular formation and motor nuclei of cranial nerves and in the meninges. The results suggest that mineralocorticoids have wide ranging effects on different parts of the central nervous system.This work was supported by the Medical Research Council of Canada and by PHS grant NS09914. We thank Ms Brenda McClain for technical assistance.     

Cilia in stellate neurons of the rat cerebellum

Summary Cilia in stellate neurons of the normal rat cerebellum are described. 8 cilia were observed in a total of 60 cells studied. An 8+1 pattern was found throughout their length. Furthermore, no arms, spokes or other accessory structures necessary for ciliary motion were seen. These findings make it possible to suggest that these cilia are probably without function and are related to the epithelial origin of these cells.This work was granted by INIC: Centro de Morfologia Experimental (MbP₁).Acknowledgments. The authors thank M.A. Rodrigues, M. M. Pacheco, M. C.Pinho and L. B. Nunes for technical assistance.     

Mechanical simulation of renal pelvic wall peristalsis in the rat

Summary A urinary concentrating defect was induced in Munich-Wistar rats by removing the renal pelvis from 1 kidney. This defect was partially corrected by crudely simulating the actions of pelvic wall peristalsis with a mechanical system that cyclically compressed the exposed renal papilla.A portion of this work was conducted at The Mount Desert Island Biological Laboratory, Salsbury Cove, Maine and was supported by NIH grant 2 RO1-AM15972-10 awarded to Dr B. Schmidt-Nielsen. Additional support came from the Maine and Pennsylvania Affiliates of the American Heart Association.     

Vitamin C and the immune response

Summary The inclusion of vitamin C in the drinking water of BALB/c mice was without effect on the humoral antibody response to sheep red blood cells and bacterial lipopolysaccharide. However, there was a significantly increased cell-mediated immune response as determined by increased T-lymphocyte responses to concanavalin A. This might suggest a mechanism, along with interferon enhancement, for the possible protection by vitamin C against some viral infections.We thank Miss Wendy Treat for excellent technical assistance.     

A quantitative study of the catecholamine-fluorescence in the ganglion paracervicale uteri of the rat

Summary In the ganglion paracervicale uteri of the rat, there are principle neurons which are able to take up offered catecholamines. Normally there is an inverse relationship between their size and their mean catecholamine-fluorescence. A comparison with the catecholamine-fluorescence of depleted and repleted adrenergic perikarya in the ganglion cervicale superius is made.Acknowledgments. I am very obliged to Dr G. Krinke and to Mrs K. Schnider for their continued interest and practical assistance. The study was supported in part by CIBA-GEIGY, Ltd. Basle.     

The chemokinetic effect of serum albumin

Summary Experiments performed by means of time lapse cinematography or the filter technique show that human serum albumin has marked chemokinetic effects on neutrophil cultured in Gey's solution. The average speed of the cells, as well as the proportion of neutrophils showing locomotion, is increased. Enhanced locomotion correlates with decreased attachment to the substratum as determined by morphological and functional criteria.We thank Mrs R. Graf and Miss M. Schuster for technical assistance. This work was supported by the Swiss National Science Fondation.     

Reversible impairment of hepatobiliary function induced by streptozotocin in the rat

Summary The effect of streptozotocin (SZ) on hepatobiliary function was studied in rats on the 1st, 7th and 15th days of treatment. Serum glucose increased significantly on the 1st day, and then remained high. Bile flow, bile acids output and BSP biliary excretion were significantly decreased on the 1st day of treatment, whereas serum sorbitol dehydrogenase was increased. All the parameters tested apart from serum glucose tended to normalize with time. The results suggested a transient toxic effect of SZ on the hepatocyte.Acknowledgment. This study was supported by a Research Grant from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), República Argentina. Joaquín V. Rodriguez is gratefully acknowledged for doing the chromatographic analyses of sulfobromophthalein, José M. Pellegrino for performing bile acids determination, and Mr. Raúl A. Trbojevich for surgical assistance.