Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CO2 central chemoreceptors play an important role in cardiorespiratory control. They are highly sensitive to P(CO2) in a broad range. These two sensing properties seem paradoxical as none of the known pH-sensing molecules can achieve both. Here we show that cultured neuronal networks are likely to solve the sensitivity versus spectrum problem with parallel and serial processes. Studies were performed on dissociated brainstem neurons cultured on microelectrode arrays. Recordings started after a 3 week initial period of culture. A group of neurons were dose-dependently stimulated by elevated CO2 with a linear response ranging from 20 to 70 Torr. The firing rate of some neurons increased by up to 30% in response to a 1 Torr P(CO2) change, indicating that cultured brainstem neuronal networks retain high CO2 sensitivity in a broad range. Inhibition of Kir channels selectively suppressed neuronal responses to hypocapnia and mild hypercapnia. Blockade of TASK channels affected neuronal response to more severe hypercapnia. These were consistent with the pKa values measured for these K+ channels in a heterologous expression system. The CO2 chemosensitivity was reduced but not eliminated by blockade of presynaptic input from serotonin, substance P or glutamate neurons, indicating that both pre and postsynaptic neurons contribute to the CO2 chemosensitivity. These results therefore strongly suggest that the physiological P(CO2) range appears to be covered by multiple sensing molecules, and that the high sensitivity may be achieved by cellular mechanisms via synaptic amplification in cultured brainstem neurons.
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PMID:High CO2 chemosensitivity versus wide sensing spectrum: a paradoxical problem and its solutions in cultured brainstem neurons. 1712 73

The regulation of cerebral blood flow (CBF) is a complex process that is altered significantly with altitude exposure. Acute exposure produces a marked increase in CBF, in proportion to the severity of the hypoxia and mitigated by hyperventilation-induced hypocapnia when CO(2) is uncontrolled. A number of mediators contribute to the hypoxia-induced cerebral vasodilation, including adenosine, potassium channels, substance P, prostaglandins, and NO. Upon acclimatization to altitude, CBF returns towards normal sea-level values in subsequent days and weeks, mediated by a progressive increase in PO2, first through hyperventilation followed by erythropoiesis. With long-term altitude exposure, a number of mechanisms play a role in regulating CBF, including acid-base balance, hematological modifications, and angiogenesis. Finally, several cerebrovascular disorders are associated with altitude exposure. Existing gaps in our knowledge of CBF and altitude, and areas of future investigation include effects of longer exposures, intermittent hypoxia, and gender differences in the CBF responses to altitude.
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PMID:Cerebrovascular responses to altitude. 1754 54

Hypocapnia and hypercapnia constrict and relax airway smooth muscle, respectively, through pH- and calcium (Ca(2+))-mediated mechanisms. In this study we explore a potential role for the airway epithelium in these responses to carbon dioxide (CO(2)). Contractile and relaxant responses of isolated rat bronchial rings were measured under hypocapnic, eucapnic, and hypercapnic conditions. Substance P was added to methacholine precontracted bronchial rings with and without epithelium. The role of Ca(2+) was assessed using Ca(2+)-free solutions and a Ca(2+) channel blocker, nifedipine. The effects of pH were assessed in solutions with HEPES buffer. Hypocapnic challenge increased the organ bath's pH and increased bronchial smooth muscle resting tension. This effect was abolished with HEPES buffer and partially inhibited by nifedipine. Hypocapnic conditions suppressed substance P-induced epithelium-dependent relaxation, whereas hypercapnia augmented the response. The epithelial hypocapnic effect was pH dependent, whereas the hypercapnic effect was pH independent. CO(2) had no effect on the epithelial independent smooth muscle agonists methacholine and isoproterenol. In conclusion our data indicate that, in addition to the effects of pH and Ca(2+), CO(2) affects airway smooth muscle by a pH-independent, epithelium-mediated mechanism. These findings could potentially lead to new treatments for asthma involving CO(2)-sensing receptors in the airways.
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PMID:Carbon dioxide enhances substance P-induced epithelium-dependent bronchial smooth muscle relaxation in Sprague-Dawley rats. 2181 29