Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prokineticin 2 (PK2) is a neuropeptide that acts as a signaling molecule regulating circadian rhythms in mammals. We have previously reported PK2 actions on subfornical organ (SFO) neurons, identifying this circumventricular organ as a target at which PK2 acts to influence autonomic control (Cottrell GT, and Ferguson AV. J. Neurosci. 24: 2375-2379, 2004). In this study, we have examined the cellular mechanisms by which PK2 increases the excitability of SFO neurons. Whole cell patch recordings from dissociated rat SFO neurons demonstrated that the mitogen-activated protein (MAP) kinase inhibitor PD-98059 prevented PK2-induced depolarization and decreases in delayed rectifier K(+) current. PK2 also increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in 39% of dissociated SFO neurons (mean increase = 20.8 +/- 5.5%), effects that were maintained in the presence of thapsigargin but abolished by both nifedipine, or the absence of extracellular Ca(2+), suggesting that PK2-induced [Ca(2+)](i) transients resulted from Ca(2+) entry through voltage-gated Ca(2+) channels. Voltage-clamp recordings showed that PK2 was without effects on Ca(2+) currents evoked by voltage ramps, suggesting that PK2-induced Ca(2+) influx was secondary to PK2-induced increases in action potential frequency, an hypothesis supported by data showing that tetrodotoxin abolished effects of PK2 on [Ca(2+)](i). These observations suggested PK2 modulation of voltage-gated Na(+) currents, a possibility confirmed by voltage-clamp experiments showing that PK2 increased the amplitude of both transient and persistent Na(+) currents in 29% of SFO neurons (by 34 and 38%, respectively). These data indicate that PK2 influences SFO neurons through the activation of a MAP kinase cascade, which, in turn, modulates Na(+) and K(+) conductances.
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PMID:Prokineticin 2 influences subfornical organ neurons through regulation of MAP kinase and the modulation of sodium channels. 1861 63