Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the effects of substance P (SP) and calcitonin gene-related peptide (CGRP) on synaptic transmission in a pontine slice containing the parabrachial nucleus (PBN). Stimulation of the ventral, external lateral portion of the PBN elicited glutamate-mediated EPSCs in cells recorded using the nystatin perforated-patch recording technique in the external lateral, external medial, and central lateral subnuclei of the PBN. Bath application of SP or CGRP dose-dependently and reversibly attenuated the evoked EPSC. The attenuation of the EPSC induced by both of these peptides was not accompanied by changes in input resistance of PBN cells over a wide voltage range, nor did these peptides alter the inward current induced by a brief bath application of AMPA. The combined application of subthreshold concentrations of these peptides revealed a synergistic interaction in reducing the evoked EPSC. The substance P neurokinin-1 receptor antagonist CGP49823 completely and reversibly blocked both the SP- and the CGRP-induced attenuation of the EPSC. However, the rat CGRP receptor antagonist human-CGRP8-37 did not block the actions of CGRP or SP on the EPSC. Using a metabolically stable analog of SP, SP (5-11), or an endopeptidase inhibitor, phosphoramidon, we were able to demonstrate that CGRP enhances the SP effect by inhibiting an SP endopeptidase. Application of phosphoramidon also revealed an endogenous SP "tone" apparently made effective by blockade of the endopeptidase. These results suggest that SP (and CGRP indirectly through an inhibition of the SP endopeptidase) acts on presynaptic NK-1 receptors to cause an inhibition of excitatory transmission in the PBN. These results indicate an important role of endopeptidases in regulating synaptic modulation by peptides.
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PMID:Peptidergic modulation of synaptic transmission in the parabrachial nucleus in vitro: importance of degradative enzymes in regulating synaptic efficacy. 881 87

We previously reported that oxytocin (OXT), released from the dendrites of magnocellular neurons in the supraoptic nucleus (SON), acts retrogradely on presynaptic terminals to inhibit glutamatergic transmission. Here we test the hypothesis that oxytocin reduces calcium influx into the presynaptic terminal. We used nystatin perforated-patch recording in vitro to first identify the calcium channels involved in glutamatergic transmission in the SON. [omega]-Conotoxin GVIA ([omega]-CTx) and [omega]-Agatoxin TK ([omega]-Aga) both reduced evoked EPSC amplitude, while nicardipine and nickel had no effect. A combination of [omega]-CTx and [omega]-Aga completely abolished the evoked EPSCs. This depressant effect was accompanied by an increase in the paired pulse ratio with no change in the kinetics of the evoked EPSCs, AMPA currents or postsynaptic cell properties. These results suggest that presynaptic N- and P/Q-type calcium channels mediate glutamate release in the SON while L-, T- and R-type channels make little or no contribution. Oxytocin-induced reduction of the evoked EPSC was substantially occluded in the presence of [omega]-CTx but only partially in the presence of [omega]-Aga. Amastatin, an endopeptidase inhibitor that increases the level of endogenous OXT, also reduced the evoked EPSC. This amastatin effect was also occluded by [omega]-CTx and [omega]-Aga. Miniature EPSCs, which are independent of extracellular calcium, were unaffected by either [omega]-CTx or by OXT, thus further substantiating an action of both compounds on calcium channels. Therefore, dendritically released oxytocin acts mainly via a mechanism involving the N-type channel, and to a lesser extent the P/Q-type channel, to decrease excitatory transmission.
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PMID:Oxytocin retrogradely inhibits evoked, but not miniature, EPSCs in the rat supraoptic nucleus: role of N- and P/Q-type calcium channels. 1131 32