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

Tachykinins depolarize guinea pig intracardiac neurons by activating nonselective cationic channels. Recently, members of the transient receptor potential family of membrane channels (TRPC) have been implicated in the generation of G protein-coupled receptor-activated nonselective cationic currents. We have investigated whether guinea pig cardiac neurons exhibit immunoreactivity to TRPC. Our results showed that nerve fibers within guinea pig intrinsic cardiac ganglia exhibited immunoreactivity to TRPC6. After culture of cardiac ganglia whole-mount explants for 72 hours, the TRPC6-IR fiber networks were absent. Therefore, the TRPC6-IR fibers were derived from sources extrinsic to the heart. A small percentage ( approximately 3%) of intracardiac neurons also exhibited TRPC6 immunoreactivity in control preparations, and the percentage of cells exhibiting TRPC6 immunoreactivity was not changed following explant culture for 72 hours. The few intrinsic TRPC6-IR neurons also exhibited nitric oxide synthase (NOS) immunoreactivity, indicating that they were nitrergic as well. We compared the immunohistochemical staining patterns of TRPC6-IR fibers with the staining patterns of a number of other neurotransmitters or neurotransmitter synthetic enzymes that mark specific extrinsic inputs to the intrinsic cardiac ganglia. The TRPC6-IR fibers were not immunoreactive for choline acetyltransferase, tyrosine hydroxylase, or substance P. However, the TRPC6-IR fibers exhibited immunoreactivity to neuronal NOS. Therefore, we propose that the TRPC6-IR fibers within the guinea pig intrinsic cardiac ganglia are vagal sensory fibers that also contain NOS. We found, in support of this conclusion, that TRPC6-IR cells were also present in sections of nodose ganglia.
 ...
PMID:TRPC6 immunoreactivity is colocalized with neuronal nitric oxide synthase in extrinsic fibers innervating guinea pig intrinsic cardiac ganglia. 1220 56

Activation of substance P receptors, which are coupled to Galpha(q), inhibits the Kir3.1/3.2 channels, resulting in neuronal excitation. We have shown previously that this channel inactivation is not caused by reduction of the phosphatidylinositol 4,5-bisphosphate level in membrane. Moreover, Galpha(q) immunoprecipitates with Kir3.2 (J Physiol 564:489-500, 2005), suggesting that Galpha(q) interacts with Kir3.2. Positive immunoprecipitation, however, does not necessarily indicate direct interaction between the two proteins. Here, the glutathione transferase pull-down assay was used to investigate interaction between Galpha(q) and the K(+) channels. We found that Galpha(q) interacted with N termini of Kir3.1, Kir3.2, and Kir3.4. However, Galpha(q) did not interact with the C terminus of any Kir3 or with the C or N terminus of Kir2.1. TRPC6 is regulated by the signal initiated by Galpha(q). Immunoprecipitation, however, showed that Galpha(q) did not interact with TRPC6. Thus, the interaction between Galpha(q) and the Kir3 N terminus is quite specific. This interaction occurred in the presence of GDP or GDP-AlF(-)(4). The Galpha(q) binding could take place somewhere between residues 51 to 90 of Kir3.2; perhaps the segment between 81 to 90 residues is crucial. Gbetagamma, which is known to bind to N terminus of Kir3, did not compete with Galpha(q) for the binding, suggesting that these two binding regions are different. These findings agree with the hypothesis (J Physiol 564:489-500, 2005) that the signal to inactivate the Kir3 channel could be mainly transmitted directly from Galpha(q) to Kir3.
 ...
PMID:Interaction of Galphaq and Kir3, G protein-coupled inwardly rectifying potassium channels. 1729 5

Noradrenergic (NAergic) A7 neurons are involved in modulating nociception by releasing noradrenaline in the dorsal spinal cord. Since NAergic A7 neurons receive dense Substance P (Sub-P) releasing terminals from ventromedial medulla, here we tested the effect of Sub-P on them. Bath application of Sub-P induced an inward current (I(Sub-P)) in NAergic neurons, which was significantly blocked by Neurokinin 1 (NK1) receptor antagonist. The I(Sub-P) was reversed at approximately -20 mV, blocked by several TRP channel blockers, enhanced by OAG and negatively regulated by PKC. Immunohistochemistry staining showed that NAergic A7 neurons express high level of TRPC6 channel proteins, which is consistent with pharmacological properties of I(Sub-P) shown above, as TRPC6 channel is shown to be augmented by OAG and inhibited by PKC. In conclusion, the above results provide mechanism underlying postsynaptic action of Sub-P on NAergic A7 neurons and a role for TRPC6 channel in NAergic pain modulation.
 ...
PMID:Neurokinin 1 receptor activates transient receptor potential-like currents in noradrenergic A7 neurons in rats. 1946 51