Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bradykinin (BK) induces intracellular calcium ([Ca2+]i) release in Madin-Darby canine kidney (MDCK) cells. During long-term continuous BK exposure, cells become desensitized and fail to respond to a new BK stimulus. We used a protocol of repeated short-term BK addition and removal. MDCK cells were loaded with the Ca-indicator indo-1 and were exposed to BK (100 nmol/L) for 10 seconds, followed by BK removal. This cycle was repeated four to eight times while [Ca2+]i was continuously recorded. In a Ca-free bath, the cells gradually became completely desensitized to repeated BK stimuli. In the presence of 1 mmol/L or 10 mmol/L Cae, however, repeated addition of BK caused repeated [Ca2+]i transients with partial decrease of peak heights (327 and 436 nmol/L delta[Ca2+]i final) (partial desensitization). Repeated BK stimuli also led to partial desensitization (70% to 85%) to adenosine triphosphatase and carbachol (heterologous desensitization). BK also reduced peak thapsigargin response (70%), consistent with partial depletion of endoplasmic reticulum Ca pools. Our results show that MDCK cells maintain their sensitivity to BK during repeated short-term BK exposures. Available Ca3 plays a major role in modulating the degree of cellular responsiveness.
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PMID:Maintenance of bradykinin-induced intracellular calcium response of MDCK cells depends on extracellular calcium. 770 2

Fluorescence intensity was monitored from individual NG108-15 cells loaded with the Ca(++)-selective probe fura-2, and exposed to 2 microM methylmercury (MeHg). The initial effect of 2 microM MeHg was an elevation in intracellular Ca++ concentration ([Ca++]i), which was not blocked by lowering extracellular Ca++ (Ca++e), nifedipine (0.1 microM) or by Ni++ (1 mM). Addition of 100 microM Mn++ to Ca(++)-containing medium did not alter fluorescence intensity at either the Ca(++)-insensitive excitation wavelength of 360 nm or the Ca(++)-sensitive wavelength of 380 nm. Depolarization with K+ decreased the intensity at both wavelengths, indicating Mn++ entry. In the presence of Mn++, MeHg decreased the 380 nm, but not the 360 nm signal. Bradykinin (Bk) caused a transient increase in the fluorescence ratio, which was blocked by the endoplasmic reticulum Ca(++)-adenosine triphosphatase inhibitor thapsigargin. Pretreatment with Bk and thapsigargin reduced significantly the increase in ratio induced by MeHg from 21.9 +/- 3.4 to 6.9 +/- 1.8% of base line. Bk had no effect when applied after MeHg. Caffeine reduced the Bk-induced increase in [Ca++]i and the MeHg-induced increase in ratio from 21.9 +/- 3.4 to 9.0 +/- 2.1%. Thus, Bk, caffeine and MeHg all appear to release a common pool of intracellular calcium (Ca2+i). When applied after MeHg, Bk increased inositol 1,4,5-trisphosphate (IP3) by 305 +/- 27% compared to 270 +/- 29% in controls. Thus, MeHg did not induce Ca++ release by IP3 generation, nor did it block the effects of Bk by interfering with IP3 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methylmercury mobilizes Ca++ from intracellular stores sensitive to inositol 1,4,5-trisphosphate in NG108-15 cells. 789 11

In a previous publication we provided evidence of a novel neuronal pathway for the control of GnRH secretion by bradykinin. The action of bradykinin appeared to be exerted through the bradykinin B2 receptor. In this study we demonstrated that the bradykinin B2 receptor is densely localized in the arcuate nucleus, median eminence, organum vasculosum of the lamina terminalis, and preoptic area, regions known to be critical for the control of GnRH secretion. To determine the mechanism of action of bradykinin in stimulating GnRH release, we used immortalized GnRH (GT1-7) cells in vitro. Bradykinin stimulation of GnRH secretion from GT1-7 cells appears to involve activation of the phospholipase C signaling pathway and mobilization of extracellular and intracellular calcium stores. Evidence to support this contention was derived from the observations that incubation of the phospholipase C inhibitor, U-73122 with bradykinin, blocked the ability of bradykinin to stimulate release from GT1-7 cells. This effect was specific, as a nitric oxide synthase inhibitor and a cyclooxygenase inhibitor were found to have no effect on bradykinin-induced GnRH secretion, suggesting that nitric oxide and PGs do not mediate bradykinin effects. Pertussis toxin also had no effect on bradykinin action. This suggests that the bradykinin B2 receptor may be coupled to a pertussis toxin-insensitive G protein in GT1-7 cells. With respect to calcium involvement in bradykinin action, fura-2 calcium indicator studies revealed that bradykinin can rapidly increase intracellular Ca2+ levels in GT1-7 cells. A role for intracellular Ca2+ in bradykinin action was further suggested by the finding that an intracellular calcium chelator, 1,2-bis(O-aminophenoxy)]ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester, significantly attenuated the effects of bradykinin on GnRH release. The elevation of intracellular calcium by bradykinin appears to be due to mobilization of calcium from the endoplasmic reticulum, as incubation of the Ca2+-adenosine triphosphatase inhibitor thapsigarin, which depletes endoplasmic reticulum Ca2+ stores, significantly attenuated bradykinin action on GnRH release. Extracellular calcium may also be involved in bradykinin action, as the L-type Ca2+ channel blockers verapamil and nifedipine had no effect on bradykinin-induced GnRH release, whereas the nonselective Ca2+ channel blocker, nickel chloride, attenuated bradykinin-induced GnRH release. Taken as a whole, these studies demonstrate that the bradykinin B2 receptor is densely localized in key hypothalamic nuclei responsible for regulation of GnRH release, and that the mechanism of bradykinin stimulation of GnRH secretion involves activation of the phospholipase C signaling pathway, with a critical role implicated for calcium in bradykinin action in GT1-7 cells.
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PMID:Bradykinin receptor localization and cell signaling pathways used by bradykinin in the regulation of gonadotropin-releasing hormone secretion. 1049 24