Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium current modulation by the muscarinic cholinergic agonist oxotremorine methiodide (oxo-M) was examined in sympathetic neurons from the superior cervical ganglion of the rat. Oxo-M strongly inhibited calcium currents via voltage-dependent (VD) and voltage-independent (VI) pathways. These pathways could be separated with the use of the specific M(1) acetylcholine receptor antagonist M(1)-toxin and with pertussis toxin (PTX) treatment. Expression by nuclear cDNA injection of the regulator of G-protein signaling (RGS2) or a phospholipase Cbeta1 C-terminal construct (PLCbeta-ct) selectively reduced VI oxo-M modulation in PTX-treated and untreated cells. Expression of the Gbetagamma buffers transducin (Galpha(tr)) and a G-protein-coupled-receptor kinase (GRK3) construct (MAS-GRK3) eliminated oxo-M modulation. Activation of the heterologously expressed neurokinin type 1 receptor, a Galpha(q/11)-coupled receptor, resulted in VI calcium current modulation. This modulation was eliminated with coexpression of Galpha(tr) or MAS-GRK3. Cells expressing Gbeta(1)gamma(2) were tonically inhibited via the VD pathway. Application of oxo-M to these cells produced VI modulation and reduced the amount of current inhibited via the VD pathway. Together, these results confirm the requirement for Gbetagamma in VD modulation and implicate Galpha(q)-GTP and Gbetagamma as components in the potentially novel VI pathway.
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PMID:A voltage-independent calcium current inhibitory pathway activated by muscarinic agonists in rat sympathetic neurons requires both Galpha q/11 and Gbeta gamma. 1090 99

Previous work from our laboratory has shown that nonspecific kappa opioid receptor (KOR) antagonism in primary somatosensory cortex (S1) can inhibit acquisition for the forebrain-dependent associative task, Whisker-Trace Eyeblink conditioning (WTEB). Although studies have demonstrated that KOR activation can alter stimuli salience, our studies controlled for these factors, demonstrating that KOR also plays a role in facilitating learning. KOR has two distinct phases of activation followed by internalization/downregulation, that each independently activate kinases and transcription factors known to mediate task acquisition and memory consolidation respectively. The current study demonstrated that antagonism of the initial phase of KOR activation in S1 via local injections of the g-protein inhibitor, pertussis toxin (PTX), blocked initial WTEB acquisition without affecting retention of the association. In contrast, KOR late phase antagonism in S1 via local injections of the GRK3-specific antagonist, guanidinonaltrindole (GNTI), blocked retention of the WTEB association without affecting task acquisition. Consistent with the known mechanism for KOR activation, KOR protein expression in S1 was found to be decreased following WTEB training, further supporting the involvement of neocortical KOR activation with learning. Prior studies have shown that task acquisition and memory consolidation are mediated by distinct molecular processes; however, little is known regarding a potential mechanism driving these processes. The current study suggests that neocortical KOR activation mediates activation of these processes with learning. This study provides the first evidence for a time- and learning-dependent property of neocortical KOR in facilitating acquisition and consolidation of associative memories, while elucidating an unexplored neocortical learning mechanism.
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PMID:Antagonizing the different stages of kappa opioid receptor activation selectively and independently attenuates acquisition and consolidation of associative memories. 2811 27