Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medullary raphe nuclei contain putative central respiratory chemoreceptor neurones that are highly sensitive to acidosis. To define the primary stimulus for chemosensitivity in these neurones, the response to hypercapnic acidosis was quantified and compared with the response to independent changes in P(CO2) and extracellular pH (pH(o)). Neurones from the ventromedial medulla of neonatal rats (P0-P2) were dissociated and maintained in tissue culture for long enough to develop a mature response (up to 70 days). Perforated patch clamp recordings were used to record membrane potential and firing rate while changes were made in pH(o), P(CO2) and/or [NaHCO(3)](o) from baseline values of 7.4, 5 % and 26 mM, respectively. Hypercapnic acidosis (P(CO2) 9 %; pH(o) 7.17) induced an increase in firing rate to 285 % of control in one subset of neurones ('stimulated neurones') and induced a decrease in firing rate to 21 % of control in a different subset of neurones ('inhibited neurones'). Isocapnic acidosis (pH(o) 7.16; [NaHCO(3)](o) 15 mM) induced an increase in firing rate of stimulated neurones to 309 % of control, and a decrease in firing rate of inhibited neurones to 38 % of control. In a different group of neurones, isohydric hypercapnia (9 % P(CO2); [NaHCO(3)](o) 40 mM) induced an increase in firing rate of stimulated neurones by the same amount (to 384 % of control) as in response to hypercapnic acidosis (to 327 % of control). Inhibited neurones also responded to isohydric hypercapnia in the same way as they did to hypercapnic acidosis. In Hepes-buffered solution, both types of neurone responded to changes in pH(o) in the same way as they responded to changes in pH(o) in bicarbonate-buffered Ringer solution. It has previously been shown that all acidosis-stimulated neurones in the medullary raphe are immunoreactive for tryptophan hydroxylase (TpOH-ir). Here it was found that TpOH-ir neurones in the medullary raphe were immunoreactive for carbonic anhydrase type II and type IV (CA II and CA IV). However, CA immunoreactivity was also common in neurones of the hypoglossal motor nucleus, inferior olive, hippocampus and cerebellum, indicating that its presence is not uniquely associated with chemosensitive neurones. In addition, under the conditions used here, acetazolamide (100 microM) did not have a significant effect on the response to hypercapnic acidosis. We conclude that chemosensitivity of raphe neurones can occur independently of changes in pH(o), P(CO2) or bicarbonate. The results suggest that a change in intracellular pH (pH(i)) may be the primary stimulus for chemosensitivity in these putative central respiratory chemoreceptor neurones.
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PMID:Quantification of the response of rat medullary raphe neurones to independent changes in pH(o) and P(CO2). 1198 82

We tested the hypothesis that cytosolic and membrane-associated carbonic anhydrase (CA IV) are involved in renal urinary acidification and bicarbonate reabsorption in rainbow trout. With the use of homological cloning techniques, a 1,137-bp cDNA was assembled that included an open reading frame encoding for a deduced protein of 297 amino acids. Phylogenetic analysis revealed that this protein was likely a CA IV isoform. With the use of this sequence and a previously described trout cytosolic isoform [tCAc (13)], tools were developed to quantify and localize mRNA and protein for the two CA isoforms. Unlike tCAc, which displayed a broad tissue distribution, trout CA IV mRNA (and to a lesser extent protein) was highly and preferentially expressed in the posterior kidney. The results of in situ hybridization, immunocytochemistry, and standard histological procedures demonstrated that CA IV was likely confined to epithelial cells of the proximal tubule with the protein being expressed on both apical and basolateral membranes. The CA IV-containing tubule cells were enriched with Na(+)-K(+)-ATPase. Similar results were obtained for tCAc except that it appeared to be present in both proximal and distal tubules. The levels of mRNA and protein for tCAc increased significantly during respiratory acidosis (hypercapnia). Although tCA IV mRNA was elevated after 24 h of hypercapnia, tCA IV protein levels were unaltered. By using F3500, a membrane-impermeant (yet filtered) inhibitor of CA, in concert with blood and urine analyses, we demonstrated that CA IV (and possibly other membrane-associated CA isoforms) plays a role in urinary acidification and renal bicarbonate reabsorption.
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PMID:Roles of cytosolic and membrane-bound carbonic anhydrase in renal control of acid-base balance in rainbow trout, Oncorhynchus mykiss. 1657 94