Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Histamine acted on H2 receptors in rat parotid tissues and induced the amylase secretion. Immunoblot analysis by using anti-H2 receptor protein antiserum demonstrated that histamine induced the increase and decrease in the amounts of H2 receptor proteins in basolateral and intracellular membranes, respectively. 2. Short-term treatment with histamine resulted in decreases in amylase secretion, the density of H2 receptors and their affinity for the agonists during further incubation with histamine, but showed an unaltered secretory response to isoproterenol, indicating that the histamine-induced desensitization was confined to H2 receptors. 3. This treatment triggered a 20% decrease in the histamine-stimulated adenylate cyclase activity and a 40% decrease in the phosphorylation level of Gi2alpha protein in the tissues, resulting in an increase in pertussis toxin (IAP)-catalyzed ADP-ribosylation of the protein. An enhancement of cholera toxin-catalyzed ADP-ribosylation of Gs protein was observed only during the first incubation with histamine. 4. This treatment triggered a 30% decrease and a 60% increase in the histamine-stimulated activities of protein kinase A and protein phosphatase 2A in the tissues, respectively. 5. Pretreatment with okadaic acid completely blocked the histamine-induced decrease in amylase secretion and increase in IAP-catalyzed ADP-ribosylation of Gi protein. The levels of Gi2alpha and Gs alpha proteins in the tissues were not modified by histamine treatment and the level of Gi2alpha protein was not affected by pretreatment with okadaic acid, as assessed by immunoblot analyses with anti-Gi2alpha and anti-Gs alpha protein antiserum. 6. The regulation of Gi2alpha protein phosphorylation in parotid tissues plays an important role in the histamine-induced desensitization of amylase secretion.
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PMID:Mechanism underlying histamine-induced desensitization of amylase secretion in rat parotid glands. 972 67

The beta-adrenergic agonist, isoproterenol (IPR), stimulated more significantly and sensitively amylase secretion from both the tissues of 7- and 56-day-old rats than a cholinergic agonist, carbachol, at the same concentration. The EC50 value of amylase secretion with IPR decreased significantly during development but that with carbachol did not change. Estimation by measuring bindings of [3H]dihydroalprenolol and [3H]quinuclidynylbenzylate indicated the marked increases in the numbers of both beta-adrenoceptors and muscarinic receptors in the tissues during development. The affinity of beta-adrenoceptors for the agonist was also enhanced during development, but that of muscarinic receptors for the agonist was not. These developmental changes in the number and affinity of beta-adrenoceptors and muscarinic receptors paralleled those in amylase secretory response of the tissues to their agonists. The response of adenylate cyclase (AC) of the tissues to 1 microM IPR was steadily enhanced after birth. In contrast, the response of AC to 1 microM forskolin was high until 14 days old, but markedly decreased at 28 days old and thereafter maintained this level. The increase in cholera toxin-catalyzed ADP-ribosylation (AR) of stimulatory GTP binding proteins (Gs proteins) in the tissues was apparent at 14 days old, reaching a maximum at 56 days old and thereafter decreasing with age. On the other hand, pertussis toxin-catalyzed AR of inhibitory GTP binding proteins (Gi proteins) did not change after birth. Thus, the ratio of apparent levels of Gs to Gi proteins increased significantly after birth, reaching a maximum at 56 days old, but decreased rapidly till 84 days old and thereafter maintained this level. These changes in the ratio paralleled those in the response of AC to IPR. These results showed that the rapid and marked increases in the number and affinity of beta-adrenoceptors and the ratio of apparent levels of Gs to Gi proteins in rat parotid tissues during development had a key role in the enhancement of the secretory response of the tissues to beta-agonists.
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PMID:Developmental enhancement of secretory response to isoproterenol coupled with increases in beta-adrenoceptor density and Gs protein function in rat parotid tissues. 975 33

Adrenomedullin is a novel hypotensive peptide originally isolated from human pheochromocytoma and recently localized to PP cells of the pancreatic islets of Langerhans. Based on the pancreatic islet-acinar axis model, we investigated the effect of adrenomedullin on regulated exocytosis of exocrine pancreas. Using rat [125I]-adrenomedullin, specific binding sites were localized to rat pancreatic acini. We next examined the effect of adrenomedullin on 100 pM cholecystokinin (CCK)-stimulated amylase release from pancreatic acini. Adrenomedullin inhibited amylase secretion in a dose-dependent manner by approximately 50% at maximum, and the IC50 was 1.1 pM. However, adrenomedullin did not affect rat [125I]CCK binding to isolated acini or reduce the intracellular free Ca2+ concentration increased by CCK. Adrenomedullin also inhibited amylase secretion induced by 1 microM calcium ionophore A23187, suggesting that adrenomedullin inhibits stimulated amylase secretion by functioning at a step(s) distal to the ligand-receptor binding system and intracellular calcium mobilizing mechanism. In streptolysin-O permeabilized acini, 10 nM adrenomedullin shifted the calcium dose-response curve to the right, indicating that adrenomedullin inhibits calcium-induced amylase secretion by reducing calcium sensitivity of the pancreatic exocytotic machinery. In addition, pretreatment of pancreatic acini with pertussis toxin abolished the inhibitory effect of adrenomedullin on CCK-stimulated amylase secretion. These results indicate that adrenomedullin inhibits stimulated amylase secretion by reducing the calcium sensitivity of the exocytotic machinery of the pancreatic acini. A pertussis toxin-sensitive GTP-binding protein(s) is also involved in this mechanism.
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PMID:Inhibition of stimulated amylase secretion by adrenomedullin in rat pancreatic acini. 992 17

The role of intrapancreatic neurons in the action of cholecystokinin (CCK) on pancreatic exocrine secretion of the totally isolated, perfused rat pancreas was investigated. Intrapancreatic neurons were activated by applying electrical field stimulation (EFS) to the isolated pancreas for 45 min. When applying EFS, spontaneous pancreatic secretions of fluid and amylase increased until the second 15-min period of EFS and then decreased during the third 15-min period. Atropine (2 microM) notably reduced the EFS-evoked pancreatic secretions of fluid and amylase. The CCK-induced (10 pM) pancreatic secretions of fluid and amylase elevated further in the first 15-min period of EFS and then gradually resumed to the levels observed during application of CCK alone in the third 15-min period of EFS. However, the CCK-induced pancreatic secretions remained elevated even in the third 15-min period of EFS when an action of endogenous somatostatin was inhibited by cyclo-(7-aminoheptanonyl-Phe-d-Trp-Lys-Thr[BZL]) (10 nM) or pertussis toxin (200 ng/ml). EFS further elevated spontaneous exocrine secretion by the cysteamine-treated (300 mg/kg) pancreas, but this was markedly reduced, to normal levels, by infusing somatostatin (100 pM). EFS increased the numbers of immunoreactive somatostatin cells in the Langerhans' islets. The results indicate that intrapancreatic neuronal activation influences CCK-induced pancreatic secretions in a dual-phase pattern in the rat: an increase during the early phase and a decrease during the late phase. Endogenous somatostatin released from the islets appears to inhibit the enhancing effect of neuronal activation on CCK-induced pancreatic secretion. Of the intrapancreatic neurons, the cholinergic ones appear to predominate in EFS's effects on CCK-induced pancreatic secretion.
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PMID:Effects of intrapancreatic neuronal activation on cholecystokinin-induced exocrine secretion of isolated perfused rat pancreas. 1008 62

Rab3 is a subfamily of the small GTP-binding protein Rab family and plays an important role in exocytosis. Several potential effectors of Rab3, including rabphilin3 and Rims (Rim1 and Rim2), have been isolated and characterized. Noc2 was identified originally in endocrine pancreas as a molecule homologous to rabphilin3, but its role in exocytosis is unclear. To clarify the physiological function of Noc2 directly, we have generated Noc2 knockout (Noc2(-/-)) mice. Glucose intolerance with impaired insulin secretion was induced in vivo by acute stress in Noc2(-/-) mice, but not in wild-type (Noc2(+/+)) mice. Ca(2+)-triggered insulin secretion from pancreatic isles of Noc2(-/-) mice was markedly impaired, but was completely restored by treatment with pertussis toxin, which inhibits inhibitory G protein Gi/o signaling. In addition, the inhibitory effect of clonidine, an alpha(2)-adrenoreceptor agonist, on insulin secretion was significantly greater in Noc2(-/-) islets than in Noc2(+/+) islets. Impaired Ca(2+)-triggered insulin secretion was rescued by adenovirus gene transfer of wild-type Noc2 but not by that of mutant Noc2, which does not bind to Rab3. Accordingly, Noc2 positively regulates insulin secretion from endocrine pancreas by inhibiting Gi/o signaling, and the interaction of Noc2 and Rab3 is required for the effect. Interestingly, we also found a marked accumulation of secretory granules in various exocrine cells of Noc2(-/-) mice, especially in exocrine pancreas with no amylase response to stimuli. Thus, Noc2, a critical effector of Rab3, is essential in normal regulation of exocytosis in both endocrine and exocrine cells.
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PMID:Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells. 1515 48

Several studies show that C-type natriuretic peptide (CNP) has a modulatory role in the digestive system. CNP administration reduces both jejunal fluid and bile secretion in the rat. In the present study we evaluated the effect of CNP on amylase release in isolated pancreatic acini as well as the receptors and intracellular pathways involved. Results showed that all natriuretic peptide receptors were expressed not only in the whole pancreas but also in isolated pancreatic acini. CNP stimulated amylase secretion with a concentration-dependent biphasic response; maximum release was observed at 1 pM CNP, whereas higher concentrations gradually attenuated it. The response was mimicked by a selective natriuretic peptide receptor (NPR-C) agonist and inhibited by pertussis toxin, strongly supporting NPR-C receptor activation. CNP-evoked amylase release was abolished by U-73122 (PLC inhibitor) and 2-aminoethoxydiphenyl borate (2-APB) [an inositol 1,4,5-triphosphate (IP(3)) receptor antagonist], partially inhibited by GF-109203X (PKC inhibitor), and unaltered by ryanodine or protein kinase A (PKA) and protein kinase G (PKG) inhibitors. Phosphoinositide hydrolysis was enhanced by CNP at all concentrations and abolished by U-73122. At 1 and 10 pM, CNP did not affect cAMP or guanosine 3',5'-cyclic monophosphate (cGMP) levels, but at higher concentrations it increased cGMP and diminished cAMP content. Present findings show that CNP stimulated amylase release through the activation of NPR-C receptors coupled to the PLC pathway and downstream effectors involved in exocytosis. The attenuation of amylase release was likely related to cAMP reduction. The augmentation in cGMP supports activation of NPR-A/NPR-B receptors probably involved in calcium influx. Present findings give evidence that CNP is a potential direct regulator of pancreatic function.
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PMID:C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas. 1770 53


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