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)

Angiotensin II (AII)-like immunoreactivity (LIR) was detected by immunostaining in 7.5 +/- 1.1% of cells obtained by redispersion of pituitary cell aggregates from 15- to 20-day-old female rats, cultured for 5-7 days in serum-free medium supplemented with thyroid hormone and dexamethasone. Also, renin-LIR was retained in these cultures. As shown by double immunostaining of paraffin-embedded sections of the aggregates, this AII-LIR was localized only in gonadotrophs. AII-LIR was detected at least up to 5 weeks in culture. On reversed-phase, high-performance liquid chromatography (HPLC), this AII-LIR co-migrated with authentic AII. In perifused aggregate cell cultures of 15- to 20-day-old female rat pituitary maintained in serum-free medium supplemented with dexamethasone (DEX) and triiodothyronine (T3), AII stimulated GH release. AI and AIII had a similar effect. To evaluate the possible involvement of endogenous AII in the local regulation of GH release, gonadotrophs were stimulated with luteinizing hormone-releasing hormone (LHRH). LHRH displayed a transient inhibitory effect on GH release, which was followed by a rebound of GH release after withdrawal of the peptide. Treatment of aggregates with pertussis toxin reversed this inhibitory effect into a significant stimulation of GH release. In aggregates cultured in serum-supplemented medium, LHRH provoked a significant stimulation of GH release which was still followed by a post-stimulus rebound release. In hemipituitaries from 5-day-old rats, a significant stimulatory effect of LHRH on GH release was found without rebound secretion. To evaluate the possible involvement of endogenous AII in the effects of LHRH on GH release, the influence of (Sar1,Ala8)AII, a peptide AII receptor antagonist, and of DUP753, a non-peptide AII receptor blocker was tested in various in vitro conditions. The effect of LHRH on GH release in aggregates cultured either in serum-free medium supplemented with DEX and T3 or in serum-supplemented medium was not affected by (Sar1,Ala8)AII, not even after enhancing the LHRH-induced GH release by treatment of the aggregates with pertussis toxin. A hundred times lower concentration of (Sar1,Ala8)AII, however, abolished the AII-induced changes in GH release. Also DUP753 (10 microM) failed to block LHRH-induced GH release in aggregates. (Sar1,Ala8)AII also failed to block the effect of LHRH on GH release from hemipituitaries. It is concluded that LHRH has inhibitory and stimulatory effects on GH release in cultured pituitary cell aggregates.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin II is retained in gonadotrophs of pituitary cell aggregates cultured in serum-free medium but does not mimic the effects of exogenous angiotensins and luteinizing-hormone-releasing hormone on growth hormone release. 147 13

As a target site for angiotensin II (A-II), renal proximal tubule is unique in that it may be equipped with a local A-II generating system and that both basolateral and apical membranes may be accessible for A-II's action. We have recently conducted studies to examine these possibilities. With in vitro cultured proximal tubular cells, we have demonstrated de novo synthesis of angiotensinogen and renin. With isolated renal brush border membrane (BBM), we have confirmed the presence of A-II receptors and found that A-II directly stimulated BBM Na(+)-H+ exchange. In search of the signal transduction mechanism, we have found that A-II also activated BBM phospholipase A2 (PLA) and that BBM contained a pertussis toxin-sensitive guanine nucleotide binding protein (G-protein) which mediates the effects of A-II. Further studies showed that prevention of PLA activation abolished A-II's effect on Na(+)-H+ exchange, and that activation of PLA by mellitin and addition of arachidonic acid similarly enhanced Na(+)-H+ exchange activity, suggesting that PLA activation may mediate the stimulatory effect of A-II on Na(+)-H+ exchange. These results thus indicate that a local signal transduction mechanism involving G-protein mediated PLA activation exists in renal BBM which mediates A-II's effect on Na(+)-H+ exchange. Taken together, we propose that, independent of A-II in the circulation, local luminal A-II may serve as an important regulatory system on sodium transport in renal proximal tubule.
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PMID:Angiotensin II and proximal tubule sodium transport. 170 7

As a target site for angiotensin II (A-II), renal proximal tubule is unique in that it may be equipped with a local A-II generating system and that both basolateral and apical membranes may be accessible for the action of A-II. We have recently conducted studies to examine these possibilities. With in vitro cultured proximal tubular cells, we have demonstrated de novo synthesis of angiotensinogen and renin. With isolated renal brush border membrane (BBM), we have confirmed the presence of A-II receptors and found that A-II directly stimulated BBM Na+/H+ exchange. In search of the signal transduction mechanism, we have found that A-II also activated BBM phospholipase A2 (PLA) and that BBM contained a pertussis toxin-sensitive guanine nucleotide binding protein (G-protein) which mediates the effects of A-II. Further studies showed that prevention of PLA activation abolished the effect of A-II on Na+/H+ exchange, and that activation of PLA by mellitin and the addition of arachidonic acid similarly enhanced BBM Na+/H+ exchange activity, suggesting that PLA activation may mediate the stimulatory effect of A-II on BBM Na+/H+ exchange. These results thus indicate that a local signal transduction mechanism involving G-protein mediated PLA activation exists in renal BBM which mediates the effect of A-II on Na+/H+ exchange. Taken together, we propose that, independent of A-II in the circulation, local luminal A-II may serve as an important regulatory system on sodium transport in renal proximal tubule.
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PMID:Potential role for local luminal angiotensin II in proximal tubule sodium transport. 188 Oct 47

The intracellular messengers that seem to be involved in renin secretion (RS) from juxtaglomerular cells (JG) are calcium (Ca), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Unlike the majority of secretory systems, an increase in intracellular Ca concentration and calmodulin and protein kinase C activation inhibit RS. The intracellular Ca concentration in JG cells can be modified if: 1) the normal mechanisms of Ca extrusion of these cells is altered; 2) the calcium output is blocked by lanthanum; 3) the function of the voltage-sensitive Ca-channels is modified; 4) uptake or liberation of Ca from endoplasmic reticulum is modified; 5) plasmatic membrane is bypassed with calcium ionophores such as A 23187. 6) JG cells are stimulated by hormones that increase Ca and activate protein kinase C such as angiotensin II, vasopressin or alpha-1 adrenergic agonists; 7) extracellular Ca concentration increases or decreases. RS is stimulated by dibutyryl cAMP, cAMP phosphodiesterase inhibitors and by hormones and agents that activate adenylate cyclase (beta adrenergic agonists, bradykinin, histamine, forskolin and ethylcarboxamide adenosine). On the contrary, RS is inhibited by hormones and agents that inhibit adenylate cyclase such as: alpha-2 adrenergic agonists, neuropeptide Y, angiotensin II and cyclohexyladenosine. Pertussis toxin increases basal RS, blocks the inhibition by agents and hormones which inhibit adenylate cyclase and potentiate the stimulation produced by beta-adrenergic agonists. In JG cells, atrial natriuretic peptide inhibits RS, increases cGMP and decreases cAMP. The increase in cGMP correlates well with the inhibition of RS.
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PMID:[Intracellular messengers in the regulation of renin secretion]. 255 Oct 26

Inhibition of renin release by angiotensin II (ANG II) is a calcium-dependent process and is thought to reflect the calcium-mobilizing action of ANG II observed in several tissues. However, in some tissues, such as liver and vascular smooth muscle, ANG II induces cellular responses through inhibition of adenylate cyclase. We examined the possibility that ANG II-induced inhibition of renin release from the kidney is also partly mediated through adenylate cyclase inhibition, by using pertussis toxin (PT), which selectively inactivates the coupling protein Ni, which couples inhibitory hormone receptors to adenylate cyclase. Rats were injected intravenously (i.v.) with 2 micrograms/100 g PT. In isolated kidneys, perfused in an open system with a synthetic medium 3, 5 and 10 days after PT treatment, the inhibition of renin release by ANG II as well as its vasoconstrictor response were significantly attenuated. This effect, which was most pronounced at lower concentrations of ANG II, indicates that ANG II may inhibit renin release partly through inhibition of adenylate cyclase activity.
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PMID:Mode of inhibition of renin release by angiotensin II. 285 14

Recently we have shown that atrial natriuretic peptide (ANP) inhibits renin release from isolated rat renal juxtaglomerular (JG) cells. ANP in general is thought to act on its target cells by the binding to specific membrane receptors. It is the objective of this contribution to summarize our present knowledge about the sequence of events by which the occupancy of ANP receptors could lead to an inhibition of renin release from juxtaglomerular (JG) cells. It was found that ANP did not affect the intracellular concentration of calcium. ANP led to a dose dependent increase in the intracellular concentration of cyclic GMP and to a dose dependent decrease of cAMPi. Inhibition of renin release from the JG-cells by ANP was clearly correlated to the level of cGMPi and not to the level of cAMPi. Concerning the mechanism by which ANP causes a rise in cGMPi in JG-cells it was found that the effect of ANP on cGMPi was potentiated by the cGMP phosphodiesterase specific inhibitor M & B 22,948. This finding suggests that ANP enhances cGMPi by the stimulation of a guanylate cyclase rather than by the inhibition of a cGMP phosphodiesterase. Moreover, evidence was obtained that the effect of ANP on cGMP, was markedly attenuated after pretreatment of the JG-cells with pertussis toxin. Since pertussis toxin is considered to inactivate guanine nucleotide binding proteins (G-proteins), this result could indicate that ANP receptors are coupled to a guanylate cyclase via a G-protein. Experimental evidence suggests that the G-protein in question might be the inhibitory unit (Ni) of the adenylate cyclase.
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PMID:Transmembrane signalling of atrial natriuretic peptide in rat renal juxtaglomerular cells. 287 65

Previous studies have demonstrated a similarity between the ability of neuropeptide Y (NPY) and clonidine to inhibit renin release and inhibit cAMP production. We therefore compared the effects of clonidine and NPY on the excretion of sodium and water in anesthetized rats which were unilaterally nephrectomized (right kidney) 10 days prior to the experiment. On the experimental day, rats were anesthetized (nembutal) and the left kidney exposed for the intrarenal infusion of the study drugs. The lowest dose of NPY (0.3 microgram/kg per min) investigated failed to alter renal function. Clonidine (0.3 microgram/kg per min) and NPY (1 microgram/kg per min) produced a similar increase in urine volume. Only NPY increased sodium excretion and osmolar clearance. Free water clearance was only increased by clonidine. Blood pressure and creatinine clearance were similar in all groups investigated. These effects were attenuated by pretreatment with pertussis toxin (5 days). The ability of pertussis toxin to block these effects suggests that the renal effects of NPY and clonidine are coupled to a G protein, conceivably the inhibitory Gi protein of the adenylate cyclase system. The disparate effects on sodium excretion and on free water and osmolar clearance indicate that the effects of these compounds may be mediated through the inhibition of different pools of hormonally stimulated cAMP.
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PMID:Disparate effects of neuropeptide Y and clonidine on the excretion of sodium and water in the rat. 290 68

The adrenergic regulation of renin secretion was studied in renal cortical slices from control and pertussis toxin-treated rats. Pertussis toxin was used to study the role of adenylate cyclase in the control of renin release. It was observed that isoproterenol and epinephrine stimulated renin secretion and that clonidine decreased both basal and isoproterenol-stimulated renin secretion in the control group. Pertussis toxin: a) increased significantly basal renin secretion, b) displaced to the left the concentration-response curve for isoproterenol and epinephrine and magnified the response to epinephrine and c) abolished the inhibitory effect of clonidine on renin secretion. This work confirms our previous results obtained in vivo and suggests a direct effect of pertussis toxin on the cells that secrete renin.
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PMID:Pertussis toxin enhances the beta-adrenergic and blocks the alpha 2-adrenergic regulation of renin secretion in renal cortical slices. 300 89

Adenosine analogs selective for the A1 subclass of adenosine receptors, such as N6-cyclohexyladenosine (CHA), inhibit renin secretion in in vitro preparations. Ca chelation blocks the inhibitory effect, consistent with mediation by increased intracellular free Ca2+, and it has been suggested that intracellular Ca2+ could increase as a result of receptor-induced inhibition of adenylate cyclase followed by decreased Ca efflux from the renin-secreting cells. Pertussis toxin blocks receptor-induced inhibition of adenylate cyclase in many cells, and in others, it blocks receptor-induced phosphotidylinositol response. In the present studies, pertussis toxin treatment stimulated the basal renin secretory rate of rat renal cortical slices and blocked the inhibitory effect of CHA but not the inhibitory effect of K-depolarization. These data support the hypothesis that a pertussis toxin substrate, such as Ni, is involved in CHA-, but not in K-depolarization, -induced inhibition of renin secretion.
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PMID:Pertussis toxin reverses adenosine receptor-mediated inhibition of renin secretion in rat renal cortical slices. 302 86

The effects of neuropeptide Y (NPY) were studied in the isolated rat kidney, which was perfused at constant perfusion pressure with a synthetic medium. In this preparation NPY produced concentration (1-100 nM)-dependent inhibition of renin release and vasoconstriction. In kidneys perfused at constant flow, inhibition of renin release by NPY was even more pronounced, excluding a flow-dependent washout effect. The simultaneous infusion of the calcium channel antagonist methoxyverapamil (2 microM) or of the calmodulin inhibitor calmidazolium (1 microM) did not prevent these effects of NPY, suggesting that calcium-dependent reactions are not primarily involved. Inhibition of renin release by NPY was also observed in tissue pieces prepared from the hydronephrotic rat kidney, in which tubular elements are lacking. This indicates that inhibition of renin release by NPY is not dependent on the presence of macula densa cells or on changes of intrarenal hemodynamics. In isolated kidneys from rats pretreated with pertussis toxin (2 micrograms/100 g ip) both effects of NPY, renal vasoconstriction and inhibition of renin release, were almost completely abolished. The pertussis toxin-sensitive factor mediating the effects of NPY is most likely the Ni-coupling protein of the adenylate cyclase complex. Accordingly, our data suggest that NPY induces renal vasoconstriction and inhibits renin release by inhibition of adenylate cyclase activity in vascular smooth muscle and renin-producing cells.
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PMID:Neuropeptide Y inhibits renin release by a pertussis toxin-sensitive mechanism. 354 37


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