Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the exception of aldosterone, little is known about the hormonal regulation of distal nephron acidification. These experiments investigated the effects of prostaglandin E2, indomethacin, lysyl-bradykinin, 8-bromo-cyclic AMP, and forskolin on proton secretion in the major acidifying segment of the distal nephron, the medullary collecting duct from inner stripe of outer medulla. Using in vitro microperfusion and microcalorimetry, net bicarbonate reabsorption (proton secretion) was measured in rabbit medullary collecting ducts before, during, and after exposure to each test substance. PGE2 reduced proton secretion 12.2%, while the following substances stimulated proton secretion: indomethacin 14.2%; 8-bromo-cyclic AMP 34.5%; forskolin 39%. Lysyl-bradykinin was without effect. These studies demonstrate that distal nephron acidification, in addition to being stimulated by aldosterone, is significantly inhibited by the hormone PGE2. The stimulation of proton secretion by cAMP suggests that other hormones known to activate adenylate cyclase may also influence distal nephron acidification.
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PMID:Hormonal regulation of proton secretion in rabbit medullary collecting duct. 302 19

1. Isolated human eccrine sweat glands were cultured in vitro. Cells were harvested and plated onto permeable supports to form confluent cell sheets, area 0.2 cm2. These were used to study the electrogenic transepithelial transport of ions by measurement of short-circuit current (SCC). Epithelial sheets had a basal SCC of 5.89 +/- 0.62 microA cm-2 (n = 33) and a transepithelial resistance of 74.1 +/- 5.6 omega cm2 (n = 33). The transepithelial potential difference varied between -0.2 and -1.8 mV with a mean value of -0.71 +/- 0.09 mV (n = 33). 2. The basal current was abolished by addition of 10 microM-amiloride to the apical bathing solution. The concentration of amiloride which inhibited basal SCC by 50% (EC50) was 0.4 microM. Cultures prepared from the secretory coil of sweat glands, rather than from whole glands, were similarly sensitive to amiloride (EC50 = 0.8 microM). 3. Lysylbradykinin (LBK), carbachol, isoprenaline, prostaglandin E2 (PGE2) and A23187 all increased SCC in cultures from whole glands. LBK responses were obtained with basolateral and not with apical application. Furthermore LBK actions were not substantially altered by cyclo-oxygenase inhibition but showed marked desensitization upon repeated application. Sheet cultures prepared from sweat gland coils also showed SCC responses to both carbachol and LBK. Forskolin, an activator of adenylate cyclase, did not alter SCC in either type of preparation. 4. Replacement of chloride and of chloride and bicarbonate in the bathing solution did not cause attenuation of the responses to LBK or carbachol in whole-gland sheet cultures. Furthermore responses were unaffected by piretanide or acetazolamide. These results were taken to indicate that anion secretion was not the basis for the SCC responses. 5. Responses to LBK and carbachol were significantly reduced by amiloride (10 microM), this effect being reversible. No responses to LBK or carbachol were seen when N-methyl-D-glucamine (NMDG) was used to replace sodium, whereas reintroduction of sodium ions restored responsiveness to these agents. 6. The SCC responses to the muscarinic agonist carbachol and to LBK appear to be due to stimulation of amiloride-sensitive, electrogenic sodium absorption in whole-gland sheet cultures. Further it would appear that, in culture, the pleuripotential capacity of the cells is revealed since both whole-gland and secretory coil cultures exhibit some properties usually associated in vivo with duct cells. Many mammalian epithelia show electrogenic chloride secretion both in response to carbachol and LBK but also in response to activation of adenylate cyclase with forskolin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human eccrine sweat gland epithelial cultures express ductal characteristics. 325 2

Lysylbradykinin (LBK) added to the apical or basolateral side of cultured rat epididymal monolayers stimulated a rise in short-circuit current (Isc) due to anion secretion. The concentration-response relationships for the apical and basolateral applications have EC50 value of 0.001 microM. The responses to apical or basolateral application of LBK were blocked by WIN64338, a specific B2 receptor antagonist, but not by Des-Arg9,[Leu8]-BK, a specific B1 receptor antagonist, indicating that the LBK effects were mediated through B2 bradykinin receptors. Experiments to desensitize the B2 receptors by repeated stimulation have demonstrated that the responses to apical or basolateral LBK were due to discrete receptors on the apical or basolateral surface. In epithelia clamped in the Ussing chambers, addition of LBK to the apical or basolateral surface evoked release of PGE2 into the apical and basolateral bathing solutions over the first 10 min following hormone addition. LBK added to the basolateral side elicited a greater release than it was added to the apical side. Pretreatment of the epithelia with piroxicam (5 microM) abolished PGE2 release elicited by apical or basolateral LBK and abrogated the Isc induced by basolateral LBK. However, the rise in Isc induced by apical LBK was reduced by 31.3% only. The anion secretion response to apical LBK was not affected by MDL-12330A, an adenylate cyclase inhibitor, but greatly attenuated by thapsigargin, an inhibitor of intracellular Ca2+ release. However, the reverse effects were seen for basolateral LBK. It is concluded that distinct pathways are involved in the stimulation of anion secretion by apical or basolateral LBK. The response to basolateral LBK was COX-dependent, mediated by PGE2 and involves cAMP as second messenger. In contrast, the response to apical LBK is largely COX-independent, not mediated by PCE2 and involves Ca2+ as intracellular messenger.
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PMID:COX-dependent and -independent pathways in bradykinin-induced anion secretion in rat epididymis. 1206 65