Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that calcitonin gene-related peptide (CGRP) plays a counterregulatory role in subtotal nephrectomy-salt (SN-salt) hypertension through an increase in vascular responsiveness to the dilator activity of this neuropeptide. Substance P (SP) is often co-localized with CGRP in perivascular sensory nerves. To determine the role and mechanism of action of SP in SN-salt hypertension, we induced hypertension in 4- to 6-week-old male Sprague-Dawley rats (n=8) by subtotal nephrectomy and 1% saline drinking water. Sham-operated rats were given either tap water (n=9) or 1% saline to drink (n=9). Eleven to 13 days after each protocol, all rats had intravenous (for drug administration) and arterial (for continuous monitoring of mean arterial pressure [MAP]) catheters surgically implanted and were studied in the conscious and unrestrained state. Baseline MAP was significantly elevated in the SN-salt rats (157 +/- 6 mm Hg) compared with tap water--fed controls (128 +/- 3 mm Hg) and 1% saline--fed controls (132 +/- 5 mm Hg). Vehicle administration did not alter the MAP in any group. In contrast, administration of spantide-II (0.2 micromol/L in saline), an SP receptor antagonist, significantly elevated the MAP in SN-salt rats (13.9 +/- 0.8 mm Hg) compared with the tap water (1.7 +/- 1.7 mm Hg) and 1% saline controls (2.0 +/- 1.9 mm Hg). SP mRNA and peptide levels in dorsal root ganglia were not significantly different between the 3 groups. Administration of exogenous SP (12 and 24 nmol center dot L(-1) center dot kg(-1) intravenously) resulted in a significantly greater decrease in MAP in the SN-salt rats compared with both control groups. Taken together, these data suggest that in SN-salt hypertension, SP plays a counterregulatory role in the absence of an increase in its neuronal expression, thereby suggesting that one possible mechanism of this compensatory vasodilator response is enhanced vascular reactivity to SP.
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PMID:Substance P in subtotal nephrectomy-salt hypertension. 1188 78

Tachykinins are excitatory neuropeptides synthesised in neuronal and glial cells of the human central and peripheral nervous system. They participate in both physiological and certain pathological conditions, i.e. synaptic transmission, nociception and neuroimmunomodulation. Tachykinins act as excitatory neurotransmitters and/or neuromodulators and induce DNA synthesis leading to stimulation of cell division and proliferation. Their biological responses are triggered via the well-established tachykinin receptors NK1, NK2 and NK3 that belong to the G protein-coupled receptor family (GPCRs). Substance P is the most important member of the tachykinin family that constitutes the major endogenous ligand for the NK1 receptor type. The presence of functional NK1 receptors has been documented in malignant brain tumours of glial origin. It has been evidenced that SP-NK1 receptor communication is involved in glioma development and progression. It is possible because the tumour cells display SP-mediated autocrine activity, the ability of cytokines stimulation and MAP kinases activation. It has been suggested that SP receptor antagonists application might be useful in attempts directed at anti-cancer therapy.
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PMID:Substance P and its receptors -- a potential target for novel medicines in malignant brain tumour therapies (mini-review). 1784 59