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

It was shown that somatostatin (SRIF) inhibited cAMP-dependent vasoactive intestinal peptide (VIP)-stimulated prolactin (PRL) release by a GH3 clonal strain of rat pituitary tumor cells and decreased basal PRL secretion and inhibited PRL release in response to thyrotropin releasing hormone (TRH) whose action was independent of prior synthesis of cAMP. Pretreatment of these cells with pertussis toxin prevented SRIF's inhibitory effects on basal and TRH-stimulated hormone secretion as well as its VIP-stimulated responses. The blockade of SRIF's inhibitory effect on the actions of TRH or VIP was dependent on both the duration of preincubation and concentration of the toxin and was correlated with the ability of the toxin to catalyze the ADP-ribosylation of the 39,000-Da membrane protein. It is likely that this pertussis toxin substrate is involved in signal transduction of SRIF on cAMP-dependent actions of VIP and cAMP-independent action of TRH. However, the mechanism of SRIF's action on TRH is not clear, since SRIF did not affect the intracellular responses by TRH, neither intracellular Ca2+ mobilization nor the increase of 1,2-diacylglycerol formation following the breakdown of polyphosphoinositides.
 ...
PMID:Pertussis toxin blocks the inhibitory effects of somatostatin on cAMP-dependent vasoactive intestinal peptide and cAMP-independent thyrotropin releasing hormone-stimulated prolactin secretion of GH3 cells. 286 31

Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (Ni) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125I-[Tyr1]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p] greater than GTP greater than GDP greater than GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+. When pancreatic acini were treated with 1 microgram/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin binding to acinar membranes was reduced. Gpp(NH)p further decreased somatostatin binding to islet-activating protein (IAP)-treated acinar membranes. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. Furthermore, exposure of acini to IAP caused ADP ribosylation of a membrane protein with Mr = 41,000 in parallel to the inhibition of cAMP accumulation in acini. The present results suggest, therefore, that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor.
 ...
PMID:Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes. 288 15

The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study we investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. In contrast 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of forskolin, VIP, and cholera toxin but had no effect on that evoked by 8-bromo-cAMP. These observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Maximal inhibition, observed in the presence of 10(-6) M somatostatin was 48 +/- 5, 47 +/- 9, and 43 +/- 12% of control for forskolin-, VIP-, and cholera toxin-evoked release of [3H]ACh. In contrast somatostatin at 10(-6) M inhibited only 20 +/- 5% of the release of [3H]ACh stimulated by 8-bromo-cAMP. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Somatostatin inhibits cAMP-mediated cholinergic transmission in the myenteric plexus. 289 4

Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125I-[Tyr11]somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites (Kd = 0.55 +/- 0.06 nM) with a maximal binding capacity of 258 +/- 20 fmol/10(6) cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125I-[Tyr11]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide (Mr 80,000) containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation (IC50 = 0.4 nM) was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. We conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein Ni to inhibit adenylate cyclase.
 ...
PMID:Functional somatostatin receptors on a rat pancreatic acinar cell line. 289 95

Hormonal activation and inhibition of the GH4Cl1 cell adenylate cyclase complex is delineated. In the presence of the guanyl nucleotide GTP, enzyme activity was enhanced twofold by thyroliberin, sixfold by vasoactive intestinal peptide (VIP), twofold by prostaglandin E2 and twofold by isoproterenol. The diterpene, forskolin, increased, the activity 14-fold. In the presence of high GTP (400 microM) and NaCl (150 mM) concentrations, somatostatin inhibited (ED50 = 0.5 microM) the cyclase activity by 40%. In the presence of 10 microM somatostatin, the ED50 values (5 nM) for thyroliberin- and VIP-stimulated adenylate cyclase activities were shifted to 20 nM. Forskolin-elicited activation was, however, not affected by somatostatin. Cholera-toxin and pertussis-toxin pretreatment of the enzyme brought about some 20-fold and twofold activation, respectively. Inhibition by somatostatin was abolished upon pre-exposure to pertussis toxin. Mild alkylation by N-ethylmaleimide increased basal and hormone-activated adenylate cyclase while somatostatin again failed to express its inhibitory potential. Further alkylation caused a gradual decline and convergence of hormone-modulated cyclase activities towards zero. The N-ethylmaleimide-induced attenuation of thyroliberin-elicited activity was paralleled by a decrease in [3H]thyroliberin binding. Trifluoperazine and an anti-calmodulin serum reduced basal and net thyroliberin-, VIP- and forskolin-enhanced cyclase activities by some 30%, 100%, 70% and 80%, respectively. The Vmax of basal and thyroliberin-stimulated adenylate cyclase was diminished by 65%, leaving the apparent Km values (7.2 mM and 2.6 mM, respectively) for Mg2+ unaltered. Finally, the phorbol ester 12-O-tetra-decanoyl-phorbol 13-acetate (TPA) doubled the activity. This effect was counteracted by the protein kinase C inhibitor, polymyxin B, while thyroliberin-enhanced adenylate cyclase remained unaffected. In summary, we have described an adenylate cyclase with stimulatory (Rs) and inhibitory (Ri) receptors coupled to a calmodulin-sensitive holoenzyme through the Gs and Gi type of GTP-binding proteins. The ratio of the Gs to Gi is high. It appears that the GH4C1 cell adenylate cyclase is also activated by protein kinase C by interference with Gi. Apparently, thyroliberin activates the cyclase both directly through Gs and indirectly via protein kinase C stimulation.
 ...
PMID:Hormone-sensitive adenylate cyclase of prolactin-producing rat pituitary adenoma (GH4C1) cells: molecular organization. 290 68

Hormonally stimulated secretion of ACTH from AtT-20 mouse pituitary tumor cells is a cyclic AMP-mediated process. The presence of inhibitory cholinergic muscarinic receptors on these cells was recently reported, and in this study, the relationship between the activation of these receptors and the consequent inhibition of cyclic AMP formation and ACTH secretion was investigated. The muscarinic agent, oxotremorine, antagonized both cyclic AMP synthesis and ACTH secretion in response to corticotropin-releasing factor (CRF), vasoactive intestinal peptide, a 27-amino acid peptide with an N-terminal histidine and a C-terminal isoleucine amide, and forskolin. Other muscarinic agents, carbachol and bethanechol, had similar inhibitory effects. The cholinomimetics reduced basal (unstimulated) ACTH secretion without decreasing basal cyclic AMP levels, and also antagonized hormone release in response to cyclic AMP-independent agonists such as K+, A-23187, and phorbol ester. Scopolamine reversed the inhibitory effects of the muscarinic agents on basal and stimulated ACTH secretion and cyclic AMP formation. Increasing the extracellular calcium concentration reversed the muscarinic antagonism of basal and CRF-stimulated hormone release without affecting the cyclic AMP response. Pertussis toxin pretreatment attenuated the inhibitory effects of the muscarinic agents on forskolin-stimulated cyclic AMP synthesis and ACTH secretion as well as the inhibitory effect of carbachol on basal ACTH release. The data suggest that cyclic AMP is an essential mediator in the ACTH secretory pathway, but that an alternate cyclic AMP-independent ACTH pathway also exists in the clonal cells, and that both pathways may be modulated by a common postcholinergic receptor mechanism.
 ...
PMID:Inhibition of ACTH secretion in mouse pituitary tumor cells by activation of muscarinic cholinergic receptors. 299 73

The effects of pertussis toxin on the responses of rat pituitary-tumour (GH) cells to thyrotropin-releasing hormone (thyroliberin, TRH) were examined. Treatment of cells with pertussis toxin did not alter the affinity or concentration of TRH receptors, or the sensitivity of the TRH receptor to inhibition by guanine nucleotides. TRH caused an increase in low-Km GTPase activity in membrane-containing fractions from both control and pertussis-toxin-treated cells. TRH stimulation of inositol phosphate formation was insensitive to pertussis toxin. TRH caused a biphasic increase in the concentrations of cytosolic free Ca2+ as monitored by intracellularly trapped Quin 2, and this increase was the same in control and toxin-treated cultures. The toxin did not alter the increase in prolactin and growth-hormone (somatotropin) release stimulated by TRH or shift the TRH dose-response curve, and it did not affect the TRH-induced rise in prolactin synthesis measured over 24 h. However, pertussis toxin did block the ability of somatostatin and muscarinic agonists to inhibit prolactin and growth-hormone secretion stimulated by vasoactive intestinal peptide when analysed under the same conditions as those in which the TRH system was unaffected. These data indicate that the guanine nucleotide effects on TRH binding and activity are not mediated by Ni, but possibly by another member of the family of guanine-nucleotide-dependent regulatory proteins.
 ...
PMID:Thyroliberin action in pituitary cells is not inhibited by pertussis toxin. 302 9

The selective loss of glucagon sensitivity of transformed MDCK cells can be restored by differentiation inducers, a process which requires RNA and protein synthesis and glycosylation. Although the glucagon dose-response curve of normal MDCK cells resembled that of liver and kidney (Kact = 10 nM), the transformed-induced cells were 10-fold less sensitive to the hormone [activation constant (Kact) = 100 nM]. Additionally, the stimulation of cAMP synthesis by a glucagon fragment (glucagon) in transformed-induced cells was greatly reduced compared to normal cells. The adenylate cyclase regulatory components of transformed-induced MDCK cell membranes seemed unaltered compared to the parental line. Both contained equivalent amounts of cholera and pertussis toxin substrates, and soluble extracts were equally capable of reconstituting isoproterenol responsiveness of S49 cyc- membranes. However, membrane fusion studies demonstrated that the glucagon sensitivity of transformed-induced membranes could not be reconstituted with heterologous membranes. When donor transformed-induced membranes (with inactivated adenylate cyclase) were fused with acceptor HeLa membranes (normally unresponsive to glucagon and prostaglandin E), such hybrids were unresponsive to glucagon, although responsiveness to prostaglandin E was evident. Parallel hybrids with normal MDCK membranes were responsive to both glucagon and prostaglandin E. This difference could not be explained by an inhibitory effect of transformed-induced membranes on receptor-adenylate cyclase coupling under the fusion conditions: the ability of these membranes to serve as an acceptor for the reconstitution of vasoactive intestinal peptide responsiveness was identical to that of normal MDCK cells. The data suggest that the glucagon sensitivity induced in transformed MDCK cells differs significantly from that of the parental line. However, these differences cannot be explained by alterations of transformed-induced membrane components relevant to the coupling of hormone receptors to adenylate cyclase.
 ...
PMID:Decreased potency of glucagon on transformed-induced MDCK cells does not reflect an alteration of adenylate cyclase components. 365 36

In pancreatic acinar cells, the epidermal growth factor (EGF) receptor interacts with both cholera toxin- and pertussis toxin (PTX)-sensitive G proteins. In the present study, isolated rat pancreatic acini were used to investigate the effect of EGF on basal and secretagogue-induced adenosine 3',5'-cyclic monophosphate (cAMP) production and amylase release. EGF increased cAMP production and amylase release in pancreatic acini. However, cAMP accumulation and amylase release elicited by either vasoactive intestinal peptide (VIP) or forskolin were inhibited by EGF (17 nM). EGF inhibited the VIP-induced cAMP production and amylase release with a half-maximal effective concentration of 3 and 2 nM, respectively. EGF had no effect on the N6,2'-O-dibutyryladenosine-3',5'-monophosphate-stimulated amylase release, suggesting that the inhibitory effect of EGF on the VIP- and forskolin-induced cAMP production is due to inhibition of adenylyl cyclase. PTX pretreatment of the acini led to an increase of the basal, EGF-, and VIP-stimulated cAMP accumulation and amylase release, indicating that PTX-sensitive G proteins exert tonic inhibition of adenylyl cyclase even in the absence of agonist. In PTX-pretreated acini, the inhibitory effect of EGF on the VIP-induced cAMP production and amylase release was abolished. In conclusion, these results suggest that EGF inhibits secretagogue-induced cAMP production via activation of PTX-sensitive G proteins in rat pancreatic acini, whereas EGF-induced cAMP production and amylase release occurs via a PTX-insensitive pathway.
 ...
PMID:EGF inhibits secretagogue-induced cAMP production and amylase secretion by Gi proteins in pancreatic acini. 749 58

Dispersed rat pancreatic acini were used to determine the effect of galanin on the exocrine pancreas and on basal and secretagogue-stimulated amylase secretion. Basal amylase secretion and amylase release stimulated by cholecystokinin octapeptide, bombesin, 12-o-tetradecanoyl-phorbol-13-acetate (TPA), secretin, and vasoactive intestinal peptide were not affected by galanin in doses ranging from 10(-12) to 10(-6) M. Galanin, however, significantly inhibited the amylase release stimulated by sub- and supramaximal doses of carbachol. A time course study showed that the inhibition by galanin occurred during the sustained phase of carbachol-stimulated amylase secretion. The inhibitory action of galanin disappeared in acini obtained from animals pretreated with pertussis toxin (PTX). These results suggest that galanin inhibits carbachol-stimulated amylase secretion through a mechanism related to a PTX-sensitive G protein.
 ...
PMID:Effects of galanin on amylase secretion from dispersed rat pancreatic acini. 751 93


<< Previous 1 2 3 4 5 6 7 8 9 Next >>