Actions of intrahypothalamic NPY on gastric function.
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Animals↗
Biomedical subjects
J S Davison
Publications and source records attributed to J S Davison.
Opioid receptors on guinea-pig intestinal crypt epithelial cells.
1. Opioid peptides promote net intestinal absorption via two mechanisms: stimulation of Na+ and Cl- absorption and inhibition of Cl- secretion. Although these transport changes are predominantly mediated by submucosal neurones, it is currently unclear whether opioid peptides can regulate enterocyte function directly. We therefore tested the hypothesis that enterocytes have specific opioid receptors. 2. Villus and crypt jejunal epithelial cells were isolated by the distended sac method from anaesthetized guinea-pigs. Flow cytometry was used to resolve enterocytes from other cell types and to determine whether binding of a fluorescently labelled opioid antagonist, naltrexone-FITC, could be prevented by unlabelled mu- and delta-opioid receptor agonists. A population of crypt enterocytes (approximately 21%) exhibited high-affinity naltrexone-FITC binding to both mu- and delta-type binding sites that was stereoselective and sodium dependent. Villus enterocytes did not exhibit any of these characteristics. 3. Basal cAMP production was elevated in both villus and crypt cells treated with IBMX (3-isobutyl-1-methylxanthine). Villus cells did not respond to 100 nM vasoactive intestinal peptide (VIP), nor were they affected by opioid peptides. In contrast, 100 nM VIP significantly increased cAMP production in crypt epithelial cells, which was significantly reduced by both morphiceptin and D-Ser2-Leu-Enk-Thr. This opioid-mediated effect was stereoselective and blocked by the opioid receptor antagonist naltrexone. 4. These experiments suggest that enterocytes isolated from the crypt epithelium of guineapigs have both mu- and delta-types of opioid receptors. It is possible that these cells participate in opioid-mediated regulation of intestinal secretion.
1-Methyl-3-isobutylxanthine↗
The dorsal vagal complex of the ferret: anatomical and immunohistochemical studies.
To further the understanding of gastrointestinal function in this species, and in particular to advance our own work concerning central emetic pathways, the cytoarchitecture and the distribution of eight neurochemicals were studied in the ferret dorsal vagal complex (DVC; area postrema, nucleus of the solitary tract [nTS] and dorsal motor nucleus of the vagus). The cytoarchitectural features of this region in the ferret were similar to those seen in other species; however, the ferret possesses a particularly large and distinct subnucleus gelatinosus of the nTS. Dense calcitonin gene-related peptide-immunoreactivity was found in the gelatinous, interstitial and commissural subnuclei of the nTS, with lesser amounts in other regions of the DVC. Enkephalin-immunoreactivity of varying densities was found throughout the DVC. Moderate to dense galanin-immunoreactivity was observed throughout the DVC, with the exception of the subnucleus gelatinosus of the nTS, from which it was virtually absent. Dense neuropeptide Y-immunoreactivity was observed in the subnucleus gelatinosus and interstitial subnucleus, with moderate staining in other regions of the DVC. Neurotensin immunoreactivity was very sparse or absent. Immunoreactivity for serotonin was sparsely distributed throughout the DVC. Moderate somatostatin-immunoreactivity was observed over a large portion of the DVC, but was virtually absent from the gelatinosus and interstitial subnuclei. Substance P immunoreactivity was observed throughout the DVC and was particularly dense in the dorsal/dorsolateral subnucleus and the dorsal aspects of the medial and commissural subnuclei. In terms of its cytoarchitecture the DVC of the ferret is more similar to the cat than the rat, especially with regard to the area postrema and the subnucleus gelatinosus of the nTS. The distribution of neuroactive substances was largely similar to other species; however, differences were present particularly in patterns of immunoreactivity for enkephalin, serotonin, neuropeptide Y and somatostatin.
Animals↗
Effect of vagal and splanchnic nerve section on Fos expression in ferret brain stem after emetic stimuli.
Previous studies have demonstrated that intraduodenal hypertonic saline (IHS) induces dense Fos expression within two regions of the ferret dorsal vagal complex (DVC): the area postrema (AP) and the medial subnucleus of the nucleus of the solitary tract (mn). The aims of the present experiments were to determine the peripheral pathways involved in excitation of DVC neurons after IHS and the relative importance of mn and AP excitation in the emetic response to this stimulus. The emetic response and the distribution of Fos were examined after IHS in animals that had received either vagotomy alone, vagotomy and splanchnic nerve section, or sham operation. The emetic response was studied in both awake and anesthetized animals, and Fos induction was studied in anesthetized animals. Vagotomy alone or combined with splanchnic nerve section abolished the emetic response and the area of dense labeling within the mn and reduced but did not abolish the labeling in the AP. It was concluded that both the emetic reflex and the dense expression of Fos within the mn after IHS are dependent on an intact vagus nerve. The excitation of neurons in the AP after IHS is partially dependent on vagal afferents, and the residual labeling that is present in the AP of neurectomized animals may be mediated via a blood-borne route.
Amidines↗
Control of exocrine secretion in the guinea-pig pancreas by histamine H3 receptors.
The aim of this study was to investigate the possible involvement of the histamine H3 receptor in control of exocrine pancreatic secretion from the guinea-pig. In in vitro experiments, the H3 receptor agonist (R)-alpha-methylhistamine (0.01-10 microM) elicited a concentration-dependent decrease in the release of alpha-amylase. (R)-alpha-Methylhistamine concentrations above 10 microM evoked a concentration-dependent increase in alpha-amylase secretion. Application of mepyramine (1 microM) partially blocked this increase. The H3 receptor antagonist thioperanide (1 microM) blocked the effects of (R)-alpha-methylhistamine below 10 microM. Histamine and (R)-alpha-methylhistamine attenuated both protein release elicited during electrical-field stimulation and the release of tritiated choline, and these effects were reversed by thioperamide. In an in vivo study, (R)-alpha-methylhistamine increased juice secretion and total protein content of the juice by 40%. Histamine H1 and H2 receptor antagonists blocked this increase and uncovered an attenuation of the secretory parameters (juice flow 28%, total protein content 44%). This attenuation was blocked by thioperamide. These observations suggest that stimulation of the histamine H3 receptor in the pancreas results in a decreased fluid and enzyme release by inhibition of acetylcholine release from intrinsic pancreatic nerves.
Animals↗
The source and action of histamine in the isolated guinea-pig gallbladder.
We have investigated the effects of histamine on motility of the gallbladder and characterized the receptor types involved. Histamine and the histamine H1-receptor agonist, 2-thiazolylethylamine (2-TEA) contracted the isolated guinea-pig gallbladder strip in a dose dependent manner. The contractile response to histamine was shifted to the right by the H1-receptor antagonist, mepyramine. In pre-contracted gallbladder strips, the H2-receptor agonist dimaprit reduced the tension generated in a dose dependent fashion. The histamine H2-receptor antagonist, ranitidine shifted the histamine concentration effect curve to the left and attenuated the dose dependent relaxations elicited at high concentrations. The histamine H3-receptor agonist, (R)-alpha-methylhistamine (RMHA) elicited dose dependent contraction of the tissue which was significantly inhibited in the presence of mepyramine. The effects of electrical field stimulation (EFS) on the strips were not significantly altered by the presence of RMHA (10(-10) - 10(-7) M) indicating little pre-synaptic H3 activity in this tissue. Histamine immunoreactivity (IR) was detected in gallbladder whole mount preparations of the mucosa and the muscularis/serosa. The histamine IR appeared cell bound in cells of varying morphological characteristics but no IR was detected in nerve fibres or cell bodies (ganglia). Alcian blue staining was consistent with the distribution of histamine IR cells as mast cells. The results indicate that histamine is distributed in the guinea-pig gallbladder and it can regulate contractile activity via activation of H1 and H2 but not H3 receptors.
Animals↗
Oral-pharyngeal-esophageal and gastric cues contribute to meal-induced c-fos expression.
We recently demonstrated that a meal induces c-fos immunoreactivity in the dorsal motor nucleus of the vagus (DMV), the nucleus of the tractus solitarius (NTS), and the area postrema (AP) of the rat brain stem. This response was not eliminated by the cholecystokinin A (CCK-A) antagonist L-364,718, a finding suggesting that feeding induces c-fos immunoreactivity by a pathway that is largely independent of CCK-A receptor activation. Consequently, the role of alternative gastrointestinal cues in the induction of c-fos was investigated. The induction of c-fos after oral-pharyngeal and esophageal stimuli was examined by use of a sham-feeding procedure via a gastric fistula. Gastric fistula-closed and fed rats displayed c-fos immunoreactivity similar to that of meal-fed rats seen previously. Fistula-open and fed rats showed the same degree of staining in the more rostral section of NTS examined as fistula-closed and fed rats, but fewer c-fos-positive nuclei in the more caudal level of the NTS. The potential for gastric distension to induce c-fos was assessed after the inflation of a gastric balloon. Physiological inflation of the balloon produced marked c-fos induction primarily in the medial NTS.
Analysis of Variance↗
Endotoxin-induced hypotension exhibits seasonal variation: a role for the submandibular glands?
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Animals↗
Regulation of jejunal arterioles by capsaicin-sensitive nerves in Nippostrongylus brasiliensis-sensitized rats.
The mechanisms by which sensory nerves elicit dilation of serosal arterioles in the jejunum of rats sensitized to the nematode Nippostrongylus brasiliensis were studied using intravital microscopy. Capsaicin (0.002-2 micrograms), applied as a bolus topically to the serosa, produced a substantially larger dilation in the sensitized rats than in unsensitized rats. Abolition of the primary afferent nerves by neonatal treatment with capsaicin and blockade of capsaicin with the antagonist ruthenium red reduced markedly the dilator actions of capsaicin. Mast cell products are important in the actions of capsaicin, because pretreatment with dexamethasone (4 mg/kg), to eliminate mast cells by a macrophage-dependent mechanism, abrogated the actions of capsaicin. In addition, superfusion of the H1 receptor antagonist diphenhydramine (2 microM) blocked the actions of capsaicin. Neither cyclooxygenase products nor platelet-activating factor was involved in capsaicin-induced dilation. The actions of capsaicin and histamine were mediated via a nitric oxide (NO)-dependent mechanism, because superfusion of an inhibitor of NO synthase (NG-nitro L-arginine methyl ester, 10 microM) blocked their effects. This inhibition of capsaicin-elicited dilation by NG-nitro L-arginine methyl ester was prevented by L-arginine (100 microM), the substrate for NO synthase. Thus the arteriolar dilation evoked by capsaicin activation of primary afferent nerves in N. brasiliensis-sensitized rats involves predominantly the release from mast cells of histamine, which then dilates the vessels by a NO-dependent mechanism.
Animals↗
The involvement of sympathetic nerves in plasma extravasation induced by prostaglandin E2 and substance P.
The effects of intravenous injection of prostaglandin E2 (PGE2), substance P (SP) and a metabolically stable SP analogue, [pGlu5,Me-Phe8,Sar9]-SP (5-11) on plasma extravasation of albumin in the rat after blockade of prostaglandin synthesis with indomethacin or chemical sympathectomy with guanethidine were studied. Blood pressure was decreased by all agonists, but only the hypotensive effects of SP were enhanced by pretreatment with indomethacin and guanethidine. The increase in plasma extravasation induced by PGE2 in the tongue, skin and lungs was blocked by both guanethidine and indomethacin. Pretreatment of the rats with guanethidine or indomethacin increased extravasation induced by SP in the tongue-tip, dorsal skin and foot, but decreased the enhanced permeability in the pinna, and did not alter the actions of the peptide in other tissues. In contrast, both guanethidine and indomethacin pretreatment increased vascular permeability responses to [pGlu5,Me-Phe8,Sar9]-SP (5-11) administration in 9 and 14 of 16 tissues examined, respectively. Thus, intact sympathetic nerves and functional cycloxygenase activity exert inhibitory constraints on the vascular permeability effects of intravenously administered SP or its analogue. On the other hand the integrity of the sympathetic nerves and prostaglandin synthesis are required for PGE2-induced increases in vascular leak.
Amino Acid Sequence↗
Gastric distention induces c-fos immunoreactivity in the rat brain stem.
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Animals↗
Neuroendocrine regulation of inflammation and tissue repair by submandibular gland factors.
Interactions between the immune, nervous and endocrine systems are important in inflammation and tissue repair. One neuroendocrine pathway involves polypeptide factors derived from the submandibular glands, whose synthesis and release are controlled by cervical sympathetic nerves. This novel pathway of immune-neuroendocrine communication is the cervical sympathetic trunk-submandibular gland (CST-SMG) axis. Here, Ronald Mathison, Joseph Davison and Dean Befus discuss the contributions of this axis to the neuroendocrine regulation of inflammation and tissue repair.
Animals↗
Fos expression in ferret dorsal vagal complex after peripheral emetic stimuli.
The aim of this study was to investigate neuronal activation in the dorsal vagal complex of the halothane-anesthetized ferret after peripheral emetic stimuli. Neuronal activity was studied by examining the distribution of the nuclear phosphoprotein Fos using immunohistochemistry. The emetic stimuli used were electrical stimulation of the supradiaphragmatic vagal communicating branch (SVCB) or intraduodenal injection of hypertonic saline. Electrical stimulation of the SVCB induced the densest Fos expression within the medial subnucleus of the nucleus of the solitary tract. After hypertonic saline injection, the greatest density of Fos-positive nuclei was observed within the area postrema and also in the medial subnucleus of the nucleus of the solitary tract. It was concluded that the emetic response to hypertonic saline involves neurons in both the area postrema and the nucleus of the solitary tract, especially the medial subnucleus, and that the medial subnucleus is important in the emetic response to SVCB stimulation.
Animals↗
Temporal analysis of the anti-inflammatory effects of decentralization of the rat superior cervical ganglia.
Bilateral decentralization of the superior cervical ganglia (SCG) reduced the pulmonary inflammation that develops 4-8 h after induction of anaphylaxis in Nippostrongylus brasiliensis-sensitized rats. Histamine levels in peritoneal lavage fluid and rat mast cell protease type II in serum were increased to comparable levels in sham-operated and decentralized rats. In vitro stimulation of alveolar macrophages (ALM) with lipopolysaccharide (LPS) provoked tumor necrosis factor-alpha (TNF-alpha) release that was two to three times greater with unchallenged decentralized rats than with sham-operated rats. However, after allergen challenge LPS-stimulated TNF-alpha release from ALM of sham-operated rats increased threefold and lasted at least 24 h, whereas with decentralized rats release of this cytokine actually decreased at 4 and 8 h. The increase in the phagocytosis and respiratory burst of circulating neutrophils seen at 4 and 8 h after allergen challenge in sham-operated rats was reduced significantly by decentralization. These results suggest that the attenuation of anaphylaxis-induced pulmonary inflammation that occurs with decentralization of the SCG is primarily associated with downregulation of neutrophil and macrophage functions.
Anaphylaxis↗
Altered vascular permeability responses to substance P in diabetic rats: interactions with a nitric oxide synthesis inhibitor.
The effect of inhibiting nitric oxide synthase (N omega-nitro-L-arginine) on plasma extravasation induced by intravenously administered substance P, [pGlu5,Me-Phe8,Sar9]substance P-(5-11) or prostaglandin E2 was examined. Control rats were more responsive than diabetic rats to both substance P and [pGlu5,Me-Phe8,Sar9]-substance P-(5-11). N omega-Nitro-L-arginine blocked the actions of substance P on dorsal skin, but potentiated those of [pGlu5,Me-Phe8,Sar9]substance P-(5-11) in control rats. In diabetic rats N omega-nitro-L-arginine, which did not affect the actions of the substance P analogue, exerted complex effects on substance P induced plasma extravasation giving potentiation in the tongue, inhibition in bronchioles, and no effect in other tissues. N omega-Nitro-L-arginine inhibited prostaglandin E2 induced extravasation in control, but not diabetic rats. The altered plasma extravasation in diabetic rats may be due to diabetes induced alterations in nitric oxide synthesis or in the responses of the endothelial cells to nitric oxide.
Amino Acid Oxidoreductases↗
Involvement of L-arginine-nitric oxide pathways in neural relaxation of the sphincter of Oddi.
To evaluate if L-arginine-nitric oxide-pathways are involved in the neural relaxation of the sphincter of Oddi, we studied the effect of nitric oxide synthase inhibition on electrical field stimulation-induced relaxation of the sphincter of Oddi in the guinea pig in vitro. After incubation with atropine (1 microM), phentolamine (1 microM) and propranolol (1 microM), histamine (50 microM) and cholecystokinin-octapeptide (25 nM) produced similar increases in sphincter tone. Subsequent field stimulation induced sphincteric relaxation, that was significantly greater when the initial tone had been raised by cholecystokinin (5 Hz, 59 +/- 9%; 10 Hz, 79 +/- 9%) compared to histamine (5 Hz, 27 +/- 3%; 10 Hz, 40 +/- 7%). N-omega-Nitro-L-arginine methyl ester (L-NAME, 100 microM), which competitively inhibits nitric oxide synthase, markedly suppressed this relaxation. The subsequent addition of L-arginine (1 mM), but not D-arginine (1 mM), restored the relaxation. Hexamethonium (100 microM) did not affect the relaxation, but tetrodotoxin (1 microM) completely abolished it. Sodium nitroprusside caused a dose-dependent relaxation of the sphincter (ED50 13 nM), which was unaffected by L-NAME. In conclusion, endogenous nitric oxide synthase products represent a major transmitter of non-adrenergic non-cholinergic relaxation of the sphincter of Oddi in the guinea pig. This relaxation is partially facilitated by cholecystokinin.
Amino Acid Oxidoreductases↗
Decentralization of the superior cervical ganglia inhibits mast cell mediated TNF alpha-dependent cytotoxicity. 1. Potential role of salivary glands.
Decentralization or ganglionectomy of the superior cervical ganglia (SCG) reduces pulmonary inflammation, as well as chemotaxis and activation of circulating neutrophils. However, the protective effect of decentralization was abolished when combined with removal of the submandibular glands (sialadenectomy) in the same animals. Thus, it has been postulated that the submandibular glands (SMG) release an anti-inflammatory factor(s) that is controlled by cervical sympathetic nerves. Decentralization of SCG did not modify in vitro histamine release or in vivo levels of rat mast cell protease II, but it reduced mast cell (MC)-mediated tumor necrosis factor alpha (TNF alpha)-dependent cytotoxicity. Combined decentralization/sialadenectomy abrogated the inhibition of MC cytotoxic activity, as we have shown previously for pulmonary inflammation and neutrophil functions. However, sialadenectomy alone inhibited MC-mediated TNF alpha-dependent cytotoxicity, an observation which suggests that SMG produce a factor(s) that can potentiate MC cytotoxic activity. Studies of the effects of SMG-derived factors, such as epidermal growth factor, nerve growth factor, and transforming growth factor beta (TGF beta), showed that only pretreatment of MCs with TGF beta 10(-8) g/ml inhibited MC-mediated TNF alpha-dependent cytotoxicity. Thus, the modulation of MC-mediated TNF alpha-dependent cytotoxicity by cervical sympathetic innervation and SMG is complex and distinct from the modulation of pulmonary inflammation and neutrophil functions identified previously.
Animals↗
Capsaicin sensitive nerves in the jejunum of Nippostrongylus brasiliensis-sensitized rats participate in a cardiovascular depressor reflex.
Superfusion of capsaicin onto the serosal surface of jejunum of Nippostrongylus brasiliensis-sensitized rats induces a short-lasting (1-3 min), dose-dependent (2 to 20 micrograms) decrease in blood pressure which ranges from -5.3 +/- 1.4% to -22.6 +/- 2.2%. The hypotension evoked by capsaicin was more marked in sensitized rats than in unsensitized animals, which responded only to the highest dose (20 mg) of capsaicin tested. The hypotensive effects of capsaicin were not affected by intravenous injections of mepyramine (10 mg/kg), a histamine receptor antagonist, or by the cyclooxygenase inhibitor indomethacin (10 mg/kg). However, an intravenous injection of a platelet-activating factor (PAF) antagonist, BN 52021 (20 mg/kg), or an intraperitoneal injection of guanethidine (8 mg/kg) 18 h prior to experimentation, to functionally impair the sympathetic nerves, abolished the capsaicin-induced drop in blood pressure. Treatment of neonatal rats with capsaicin reduced by 75% the hypotensive effects of capsaicin, whereas the capsaicin antagonist, ruthenium red, reduced non-significantly the hypotensive action of capsaicin. It is concluded that the activation of jejunal sensory nerves in N. brasiliensis-sensitized rats by capsaicin induced a reflex hypotension that is dependent upon PAF release from mast cells and functional sympathetic nerves. In addition, the afferent function of the sensory nerves are not totally blocked by ruthenium red as capsaicin elicits the reflex hypotension in the presence of this blocker of sensory nerve efferent function.
Anaphylaxis↗