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)

Hypoxic stimulation of carotid body chemoreceptors is conveyed to the brainstem by primary sensory neurons whose peripheral axons run in the carotid sinus nerve. While considerable attention has focused on defining chemical neuroregulators released by glomus cells in the carotid body, our understanding of the morphology, distribution and transmitter phenotype of these carotid body afferent neurons remains limited. Carotid body afferent neurons were labeled by microinjection of the retrograde tracer, Fluorogold, into the vascularly isolated rat carotid body. In addition, immunoelectron microscopy was used to correlate transmitter phenotype with ultrastructural features of afferent terminals in the carotid body. Our results indicate that 41% of all carotid body afferent neurons express tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, whereas 7% contain substance P. Tyrosine hydroxylase- and substance P-positive neurons constitute separate subpopulations of carotid body afferents, as these two phenotypes were not colocalized. Most of the tyrosine hydroxylase-containing carotid body afferent neurons were small- or medium-sized (mean cell diameter 15-20 microns) and located in the distal petrosal ganglion, whereas the majority of substance P-containing carotid body afferent neurons were medium- to large-sized (mean cell diameter 20-29 microns) and located in the proximal petrosal ganglion and jugular ganglion. These differences strengthen the notion that these catecholaminergic and peptidergic carotid body afferent neurons give rise to functionally distinct subsets of chemoafferent fibers. To further characterize the catecholaminergic phenotype expressed by tyrosine hydroxylase-positive cells in the petrosal ganglion, we examined the colocalization of tyrosine hydroxylase and DOPA decarboxylase, the dopamine-synthesizing enzyme. Eighty-six per cent of tyrosine hydroxylase-positive neurons in the distal petrosal ganglion also contained DOPA decarboxylase; as these cells do not express the norepinephrine-synthesizing enzyme, dopamine beta-hydroxylase, these data indicate that the catecholaminergic carotid body afferent neurons are dopaminergic. Finally, ultrastructural analysis of the peripheral processes of tyrosine hydroxylase-positive afferent terminals in the carotid body demonstrated endings in close opposition to Type I glomus cells, consistent with a role for dopaminergic afferent neurons in carotid body chemoreception. One possibility is that these cells, in addition to their role as afferents, constitute a morphologic substrate for dopaminergic "efferent" inhibition in the carotid body.
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PMID:Transmitter diversity in carotid body afferent neurons: dopaminergic and peptidergic phenotypes. 128 13

In the present study, we tested the hypothesis that substance P (SP) is an excitatory peptide to the rat carotid body and plays an important role in chemosensory excitation by hypoxia. Chemosensory discharge was recorded from the cut carotid sinus nerve in 19 anaesthetized, paralyzed and mechanically ventilated rats. Intracarotid administration of SP augmented the chemoreceptor activity in a dose-dependent manner. Maximal excitation was seen with 10 nmol SP. Carotid body stimulation by SP was independent of its effects on arterial blood pressure. The effect of SP antagonists, D-Pro2-D-Trp7,9-SP (DPDT-SP) or Spantide, on chemoreceptor responses to SP and hypoxia was examined in 12 rats. Close carotid body administration of either antagonist at doses of 40 micrograms.kg-1.min-1 elicited an augmentation followed by a progressive depression of baseline carotid body activity. SP antagonists significantly reduced peptide-induced carotid body stimulation and also markedly attenuated the chemoreceptor response to hypoxia. Systemic administration of sodium bicarbonate stimulated the carotid bodies, presumably by releasing CO2, and the bicarbonate-induced chemoreceptor stimulation was not affected by SP antagonists. From these results we conclude that in rats (a) SP stimulates the carotid bodies independently of its effects on arterial blood pressure, and (b) SP is associated with the chemosensory stimulation by hypoxia but not with other excitatory stimuli.
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PMID:Tachykinin antagonists in carotid body responses to hypoxia and substance P in the rat. 752 Jan 91

Carotid body expresses neutral endopeptidase (NEP)-like enzyme activity and phosphoramidon, an inhibitor of NEP augments sensory response of the carotid body to hypoxia (Kumar et al., 1990). NEP hydrolyzes substance P (SP) and methionine enkephalin (Met-ENK) in the nervous system. In the present study, we determined whether NEP hydrolyzes Met-ENK and SP in the carotid body and whether these peptides contribute to the phosphoramidon-induced potentiation of the sensory response to hypoxia. Experiments were performed on carotid bodies excised from anaesthetized adult cats. HPLC analysis showed that both SP and Met-ENK were hydrolyzed by the carotid body. Phosphoramidon (400 microM) markedly inhibited SP (approximately 90%) but had only marginal effect on Met-ENK hydrolysis (approximately 15%). Sensory responses of the carotid body in vitro to hypoxia (pO2, 68 +/- 6 mmHg) and SP (10 nmoles) were potentiated by phosphoramidon by approximately 80% and approximately 275% respectively (p < 0.01). SP-receptor antagonist abolished phosphoramidon-induced potentiation of the sensory response to hypoxia as well as to SP. These results demonstrate that SP is a preferred substrate for NEP in the carotid body and SP plays a major role in the potentiation of the hypoxic response of the carotid body by phosphoramidon.
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PMID:Role of substance P in neutral endopeptidase modulation of hypoxic response of the carotid body. 1084 12

Carotid body glomus cells produce and release acetylcholine (ACh), catecholamines, and neuropeptides, and there is biochemical evidence that these cells possess receptors for these substances. Thus, we studied the effects of cholinergics [ACh, nicotine (Nic), bethanechol (BN)] and peptides [met-enkephalin (ME), substance P (SP)] on the membrane potential (Em), voltage noise (Erms), and input resistance (Ro) of glomus cells. Sliced carotid bodies (for cell visualization) of cats, rabbits, and mice were used. The mean Em and Ro of rabbit glomus cells were lower than those of cat and mouse. Ro of mouse cells was the largest, whereas Erms was similar in all species. The various agents had qualitatively similar effects on the cells of the three species although some quantitative differences were sometimes observed. But, for simplicity, results were pooled. ACh depolarized most cells (effect depressed by zero [Ca2+]o and Mn2+), reduced their resistance, and induced variable changes in Erms. Different ACh doses produced non-linear effects on DeltaEm. Nic and BN also depolarized most cells, reducing Ro and Erms. Atropine depressed the cell responses to BN; alpha-bungarotoxin the depolarizing response to Nic. ME and SP depolarized most cells, but only ME significantly reduced Ro. Neither peptide significantly changed voltage noise. Comparing the effects of all drugs showed that BN was the most effective depolarizing agent, producing the largest reductions in Ro. There were negative correlations between DeltaEm and DeltaRo with the cholinergics and SP; correlations between DeltaErms and DeltaRo were significant and positive only with the cholinergics. These results confirm the presence of nicotinic, muscarinic, and peptidergic receptors in glomus cells. The similar effects of cholinergics and peptides and those of flow interruption and anoxia suggest that the latter may partly act via autoreceptors for the released transmitters.
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PMID:Effects of Putative Neurotransmitters of the Carotid Body on its Own Glomus Cells. 1210 5