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)

The effects of the potassium channel activators (KCA) levcromakalim and RP52891 on NANCe nerve-mediated changes in pulmonary dynamics were investigated in the anaesthetized guinea-pig, using a newly-developed respiratory dynamics computer. Levcromakalim (0.025-0.2 mg/kg i.v.) and RP52891 (0.05-0.5 mg/kg i.v.) caused dose-dependent inhibition of NANCe nerve-mediated increases in airways resistance (RAW) and decreases in dynamic compliance (Cdyn). These effects of the KCAs persisted for at least 1 h. Unlike NANCe nerve-mediated responses, equivalent challenges with exogenously-administered substance P (SP; 10-25 micrograms/kg i.v.) and neurokinin A (NKA; 0.5-2.0 micrograms/kg i.v.) tended to produce progressively increasing responses but this effect was not statistically significant. Levcromakalim (0.2 mg/kg i.v.) and RP52891 (0.5 mg/kg i.v.) did not significantly decrease responses to exogenously-administered SP, although NKA-induced bronchoconstriction was attenuated. Glibenclamide (25 mg/kg i.v.) partially reversed the NANCe-inhibitory effects of levcromakalim (0.1 mg/kg i.v.) and RP52891 (0.25 mg/kg i.v.) and fully reversed their hypotensive effects. We have shown that levcromakalim and RP52891 inhibit bronchoconstrictor responses to NANCe nerve stimulation. This involves the opening of a glibenclamide-sensitive K(+)-channel and may represent effects at a pre-junctional site on NANCe neurones to reduce transmitter release.
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PMID:Effects of levcromakalim and RP52891 on NANCe nerve-mediated changes in pulmonary dynamics evoked by vagal stimulation in the guinea-pig. 821 74

1. Opioid agonists inhibit neurogenic mucus secretion in the airways. The mechanism of the inhibition is unknown but may be via opening of potassium (K+) channels. We studied the effect on neurogenic secretion in ferret trachea in vitro of the OP1 receptor (formerly known as delta opioid receptor) agonist [D-Pen2,5]enkephalin (DPDPE), the OP2 receptor (formely kappa) agonist U-50,488H, the OP3 receptor (formerly micro) agonist [D-Ala2, N-Me-Phe, Gly-ol5]enkephalin (DAMGO), the ATP-sensitive K+ (K(ATP)) channel inhibitor glibenclamide, the large conductance calcium activated K+ (BK(Ca)) channel blocker iberiotoxin, the small conductance K(Ca) (SK(Ca)) channel blocker apamin, the K(ATP) channel opener levcromakalim, a putative K(ATP) channel opener RS 91309, and the BK(Ca) channel opener NS 1619. Secretion was quantified by use of 35SO4 as a mucus marker. 2. Electrical stimulation increased tracheal secretion by up to 40 fold above sham-stimulated levels. DAMGO or DPDPE (10 microm each) significantly inhibited neurogenic secretion by 85% and 77%, respectively, effects which were reversed by naloxone. U-50,488H had no significant inhibitory effect on neurogenic secretion, and none of the opioids had any effect on ACh-induced or [Sar9]substance P-induced secretion. 3. Inhibition of neurogenic secretion by DAMGO or DPDPE was reversed by iberiotoxin (3 microM) but not by either glibenclamide or apamin (0.1 microM each). Iberiotoxin alone did not affect the neurogenic secretory response. 4. Levcromakalim, RS 91309 or NS 1619 (3 nM-3 microM) inhibited neurogenic secretion with maximal inhibitions at 3 microM of 68%, 72% and 96%, respectively. Neither levcromakalim nor RS 91309 at any concentration tested significantly inhibited acetylcholine (ACh)-induced secretion, whereas inhibition (60%) was achieved at the highest concentration of NS 1619, a response which was blocked by iberiotoxin. 5. Inhibition of neurogenic secretion by levcromakalim (3 microM) or RS 91309 (30 nM) was inhibited by glibenclamide but not by iberiotoxin. In contrast, inhibition by NS 1619 (30 nM and 3 microM) was blocked by iberiotoxin but not by glibenclamide. 6. We conclude that, in ferret trachea in vitro, OP1 or OP3 opioid receptors inhibit neurogenic mucus secretion at a prejunctional site and that the mechanism of the inhibition is via opening of BK(Ca) channels. Direct opening of BK(Ca) channels or K(ATP) channels also inhibits neurogenic mucus secretion. In addition, opening of BK(Ca) channels inhibits ACh-evoked secretion of mucus. Drugs which open BK(Ca) channels may have therapeutic anti-secretory activity in bronchial diseases in which neurogenic mechanisms and mucus hypersecretion are implicated in pathophysiology, for example asthma and chronic bronchitis.
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PMID:Neuroregulation of mucus secretion by opioid receptors and K(ATP) and BK(Ca) channels in ferret trachea in vitro. 960 70