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)

The physiological regulation of intestinal proglucagon-derived peptide secretion has not been well studied. We have therefore used a fetal rat intestinal cell culture model to investigate the control of secretion of the gut glucagon-like immunoreactive (GLI) peptides by other intestinal regulatory peptides in vitro. Secretion of the intestinal GLI peptides was found to be stimulated in a dose-dependent fashion by the intestinal endocrine peptide, gastric inhibitory peptide (at greater than or equal to 10(-10) M, P less than 0.05), and by the neurocrine peptides, gastrin-releasing peptide (at greater than or equal to 10(-12) M, P less than 0.05), and calcitonin gene-related peptide (at greater than or equal to 10(-8) M, P less than 0.05). Gastrin-releasing peptide and its amphibian equivalent, bombesin were equipotent in stimulating GLI peptide secretion. In contrast, the endocrine and neurocrine intestinal somatostatin-related peptides, somatostatin-28 and -14, inhibited release of the GLI peptides, at concentrations of 10(-10) (P less than 0.01) and 10(-8) (P less than 0.01) M, respectively, with significant differences in potency between the two peptides detected at 10(-10) M (P less than 0.05). The inhibitory effects of both somatostatin-28 and -14 could be blocked by preincubation of the cells with pertussis toxin (P less than 0.05). Dose-dependent stimulation of gut GLI peptide secretion was also detected in response to treatment of cultured cells with sodium oleate (at 10(-4) M; P less than 0.05), or with the cholinergic agonist bethanecol (at greater than or equal to 100 microM; P less than 0.05). Other endocrine [cholecystokinin, glucagon, glucagon-like peptide-1(1-37), glucagon-like peptide-1(7-37), glucagon-like peptide-2, neurotensin, and peptide YY] and neurocrine (vasoactive intestinal peptide) peptides, and the synthetic glucocorticoid, dexamethasone, were without effect on secretion of the gut GLI peptides, at doses of 10(-12) to 10(-6) M. The results of the present study therefore demonstrate that secretion of the intestinal proglucagon-derived peptides is under the regulatory control of a wide variety of intestinal endocrine and neurocrine peptides, as well as nutrients (fats) and neurotransmitters (acetylcholine).
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PMID:Regulation of intestinal proglucagon-derived peptide secretion by intestinal regulatory peptides. 167 88

The cellular signaling mechanism of adenosine action has been studied in highly purified populations of cultured cells from the rabbit medullary thick ascending limb of Henle's loop (MTAL). The effects of specific adenosine-receptor agonists 5'(N-ethylcarboxamido)adenosine (NECA; A2) and N6-cyclohexyladenosine (CHA; A1) on basal and hormone-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, cytosolic free calcium concentration ([Ca2+]f), and formation of inositol phosphates were examined. Production of cAMP was stimulated by high doses of NECA and was inhibited by low doses of CHA. The inhibitory effect of CHA was observed in cells in which cAMP production was first stimulated with vasopressin, isoproterenol, prostaglandin E2 (10(-6) M), or calcitonin (100 ng/ml) and was abolished by pretreating the cells with pertussis toxin (PT) for 12-20 h. A highly selective adenosine A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), also abolished the inhibitory effect of CHA. Both NECA and CHA induced a rapid (10 s) and transient increase in [Ca2+]f, and this was associated with an increased inositol trisphosphate (IP3) production. Single-cell [Ca2+]f measurements indicated that all MTAL cells responded to CHA. The removal of extracellular Ca2+ failed to inhibit these responses. Pretreatment with PT or administration of CPX abolished both the increase in [Ca2+]f and the formation of IP3 occurring in response to CHA and NECA. Our results suggest that both adenylate cyclase-coupled inhibitory (A1) and stimulatory (A2) adenosine receptors are present in pure populations of cultured MTAL cells. Moreover, activation of an adenosine receptor coupled to a PT substrate results in the increased production of inositol phosphate and elevation of [Ca2+]f.
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PMID:Effects of adenosine on cAMP production and cytosolic Ca2+ in cultured rabbit medullary thick limb cells. 184 67

Calcitonin is a calcium regulating peptide hormone with binding sites in kidney and bone as well as in the central nervous system. The mechanisms of signal transduction by calcitonin receptors were studied in a pig kidney cell line where the hormone was found to regulate sodium pumps. Calcitonin receptors activated the cyclic adenosine monophosphate (cAMP) or the protein kinase C (PKC) pathways. The two transduction pathways required guanosine triphosphate (GTP)-binding proteins (G proteins) (the choleratoxin sensitive Gs and the pertussis toxin sensitive Gi, respectively) and led to opposite biological responses. Moreover, selective activation of one or the other pathway was cell cycle-dependent. Therefore, calcitonin may induce different biological responses in target cells depending on their positions in the cell cycle. Such a modulation of ligand-induced responses could be of importance in rapidly growing cell populations such as during embryogenesis, growth, and tumor formation.
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PMID:Cell cycle-dependent coupling of the calcitonin receptor to different G proteins. 184 55

Neuropeptide Y (NPY) is a unique peptide with wide distribution in central and peripheral nervous systems. In the guinea pig, NPY-positive fibers are prominent in the myenteric plexus. To test whether NPY inhibits myenteric plexus acetylcholine (ACh) release and to define mechanisms, a purified preparation of myenteric plexus neurons was derived from the teniae coli of neonatal guinea pigs and maintained in primary culture. Incubation of cultured neurons labeled with [3H]ACh in the presence of NPY (10(-14)-10(-6) M) significantly inhibited basal ACh release (83 +/- 16 to 58 +/- 11% of control). NPY significantly inhibited ACh release stimulated by potassium (55 mM); by adenylate cyclase agonists forskolin (10(-6) M) and cholera toxin (10(-8) M); and by calcitonin gene-related peptide, cholecystokinin octapeptide, and vasoactive intestinal peptide (each 10(-8) M). In each instance, the inhibitory effects of NPY were reversed by preincubation with pertussis toxin. Reversal of inhibitory effects by pertussis toxin suggests that the actions of NPY are mediated via an inhibitory GTP-binding protein.
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PMID:Inhibition of acetylcholine release from guinea pig myenteric neurons by neuropeptide Y: GTP-binding protein mediation. 190 63

A high density of nerve fibers containing calcitonin-gene-related peptide (CGRP) is present in the atria. Recently CGRP was reported to open ATP-sensitive K channels in arterial smooth muscle cells. This study examines whether CGRP activates a similar K+ channel in cardiac cells. In voltage-clamped whole cells loaded with GTP and ATP, CGRP reversibly evoked an inwardly rectifying K+ current. To identify the K+ channel that gives rise to this current, three types of K+ channel (resting, ATP-sensitive and acetylcholine-activated) were examined. CGRP failed to activate or inhibit the ATP-sensitive or the resting K+ channel. However, CGRP (0.1-1 microM) caused activation of single channels with kinetics similar to that of the muscarinic K+ channel (35-40 pS conductance and approx. 1 ms mean open time in symmetrical 140 mM K+). In excised, inside-out (CGRP in pipette) or in outside-out (GTP in pipette) patches, the K+ current was activated by perfusion with GTP or CGRP, respectively, suggesting that CGRP activated the muscarinic K+ channel via GTP-binding protein. Treatment with pertussis toxin inhibited the activation of the K+ channel, suggesting that CGRP receptor may be coupled to a Gi or a Go type of GTP-binding protein. Together with previous findings, these results suggest that CGRP modulates several types of ion channels to produce its cellular effects.
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PMID:Calcitonin-gene-related peptide activates the muscarinic-gated K+ current in atrial cells. 190 72

Intracerebroventricular injection of pertussis toxin (PTX, 1 microgram/rat) six days before the hot plate test abolished analgesia induced by central morphine. The toxin did not affect analgesia evoked by central neurotensin or ASU 1-7 eel calcitonin. PTX pretreatment also attenuated footshock-induced analgesia (FSIA) delivered to all four paws. When the shock was restricted to the front paws, PTX consistently lowered postshock tail flick latencies, but did not reduce analgesia resulting from shock delivered to the hind paws. It thus appears that PTX-sensitive G-proteins are an essential transduction step needed to initiate the molecular events underlying opiate analgesia evoked by either morphine or shock. In contrast, the signal transduction mechanism subsequent to the stimulation of neurotensin or calcitonin receptors, and to the nonopiate FSIA, appears not to involve PTX-sensitive G-proteins.
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PMID:Pertussis toxin pretreatment affects opiate/nonopiate and stress-induced analgesia differently. 206 92

Calcitonin inhibits osteoclastic bone resorption and its action involves two separate acute effects on the osteoclast, both essential to the action of the hormone: abolition of cell motility (Q) and marked cellular retraction (R). The former was mimicked by dibutyryl cyclic AMP and cholera toxin and the latter by pertussis toxin, ionomycin and increases in ambient calcium. Aluminium fluoride ions produced both Q and R effects, while lithium prevented both. In addition, calcitonin elicited a biphasic elevation of cytosolic-free calcium in single isolated osteoclasts. We propose that the action of calcitonin is mediated by at least two G proteins, one responsible for the Q effect and the other for the R effect. In addition, two second messengers, cyclic AMP and calcium, are involved. These findings may help to explain the potency of calcitonin in inhibiting bone resorption, and may allow the rational design of new therapeutic agents designed to alter osteoclast behaviour.
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PMID:Evidence that the action of calcitonin on rat osteoclasts is mediated by two G proteins acting via separate post-receptor pathways. 217 May 58

The two mammalian neuropeptides substance P (SP) and neurokinin A (NKA) have been demonstrated to stimulate DNA synthesis in connective tissue cells, suggesting that peripheral neurons may play a role in development and tissue regeneration. In this study we have tried to identify intracellular messengers required for SP- and NKA-induced DNA synthesis. SP and NKA, as well as platelet-derived growth factor (PDGF) stimulated formation of inositol phosphates in smooth muscle cells (SMC), whereas no effect on inositol phosphates formation occurred in response to nonmitogenic neuropeptides. Pretreatment of the cells with pertussis toxin markedly decreased DNA synthesis induced by NKA. This toxin inhibits formation of inositol phosphates by acting on a regulatory G-protein. Calcium and calmodulin antagonists also inhibited NKA-induced DNA synthesis. These results imply that the mitogenic signal(s) produced by activated neuropeptide receptors involves formation of inositol phosphate and activation of a calcium/calmodulin dependent process. We further report that other neuropeptides occurring in peripheral neurons, i.e., vasoactive intestinal polypeptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, or cholecystokinin, are without growth-stimulatory effect on cultured SMC.
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PMID:Coupling between inositol phosphate formation and DNA synthesis in smooth muscle cells stimulated with neurokinin A. 245 38

To aid in characterizing adenosine receptors in renal cells, primary cultures of rabbit cortical collecting tubule (RCCT) cells were infected with an adenovirus 12-simian virus 40 hybrid, resulting in a continuous cell line. The cells, designated RCCT-28A, retained their epithelial morphology and reacted with a monoclonal antibody specific for rabbit collecting tubule. Adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was stimulated by vasopressin (AVP), isoproterenol, prostaglandin E2 (PGE2), calcitonin, parathyroid hormone, and a potent adenosine A1- and A2-receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA). A more selective adenosine A1-receptor agonist, N6-cyclohexyl adenosine (CHA) inhibited basal and AVP-stimulated cAMP accumulation. Cytosolic free calcium was transiently elevated by bradykinin, PGE2, NECA, and CHA. To examine the mechanism by which adenosine analogues increase intracellular free calcium, phosphoinositide (PI) turnover was assessed in the 28A cells after labeling with myo-[3H]inositol. NECA and CHA increased [3H]inositol phosphate formation with an approximate half-maximal effective concentration of 0.1 microM for both analogues. The increase in PI turnover was blocked by the selective adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine and pretreatment of the 28A cells with pertussis toxin. These results suggest that adenosine analogues increase cytosolic free calcium by stimulating PI turnover.
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PMID:Adenosine-sensitive phosphoinositide turnover in a newly established renal cell line. 247 75

We have examined the regulation by prostaglandin E2 (PGE2) of hormone-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cells isolated by immunodissection from both the medullary and cortical thick ascending limb of Henle's loop of rabbit kidney. At concentrations greater than 10(-8) M, PGE2, but not sulprostone (16-phenoxy-17,18,19,20-tetranor-PGE2 methylsulfonilamide), caused cAMP accumulation in both cortical and medullary thick limb cells. However, at concentrations of less than or equal to 10(-8) M, both PGE2 and sulprostone inhibited arginine vasopressin (AVP)-, calcitonin-, and glucagon-induced cAMP accumulation in medullary thick ascending limb (mTAL) cells. In cortical thick limb (cTAL) cells, sulprostone also inhibited AVP-, calcitonin-, and parathyroid hormone (PTH)-induced cAMP accumulation. The inhibitory effects of PGE2 and of sulprostone were blocked by pretreatment of mTAL and cTAL cells with pertussis toxin. Membranes prepared from mTAL cells exhibited a [3H]PGE2 binding activity that was stimulated on addition of the stable guanosine 5'-triphosphate (GTP) analogue, 5'-guanosine gamma-thiotriphosphate (GTP gamma S); moreover, sulprostone inhibited [3H]PGE2 binding. Our results suggest that PGE2 can function via a prostaglandin E receptor linked to a guanine nucleotide regulatory protein, Gi, to attenuate hormone-induced cAMP formation in both mTAL and cTAL cells of rabbit kidney.
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PMID:Regulation of cAMP metabolism by PGE2 in cortical and medullary thick ascending limb of Henle's loop. 253 67


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