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)

Studies were conducted in young postnatal swine to determine if substance P (SP) participates in the regulation of postnatal intestinal hemodynamics and oxygenation. SP was present in homogenates of whole intestine from postnatal swine in an age-dependent manner as follows: 1 day old and never fed, 126 +/- 35; 3 days old and fasted, 148 +/- 30; and 14 days old, 51 +/- 10 pg/mg protein (P < 0.01, 14- vs. 1- or 3-day-olds). Phenylephrine-precontracted rings of mesenteric artery from 3-day-old subjects mounted for tension recording within buffer-filled myographs demonstrated brisk relaxation in response to SP (EC50, 2 x 10(-10) M). This relaxation was eliminated by mechanical removal of the endothelium or blockade with the L-arginine analog NG-monomethyl-L-arginine (L-NMMA) and was significantly attenuated by pretreatment with N-acyl-L-Trp-3,5-bis-(trifluoromethyl) benzyl ester (NATB), a highly selective NK-1 receptor antagonist (pA2 5 x 10(-10) M). Infusion of exogenous SP into the mesenteric artery of innervated in vivo gut loops reduced intestinal vascular resistance 35% and increased tissue oxygen uptake 40% in both 3- and 14-day-old subjects. By contrast, blockade of the NK-1 receptor for SP with NATB increased intestinal vascular resistance 19% in 3-day-old subjects but only 5% in 14-day-old subjects (P < 0.01). SP-induced changes in gut vascular resistance were significantly attenuated by prior coinfusion of NATB or L-NMMA, indicating that the peptide exerted this vascular effect via theNK-1 receptor, which is linked to endothelial cell nitric oxide synthase. Both NATB and L-NMMA attenuated flow-induced dilation within pump-perfused in vitro gut loops from 3-day-old subjects. SP appears to participate in the regulation of the newborn intestinal circulation, especially during the first days after birth.
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PMID:Postnatal changes in gut hemodynamics: a possible role for substance P. 969 15

Chronic inflammation associated with osteoarthritis (OA) alters normal responses and modifies the functionality of the articular vasculature. Altered responsiveness of the vasculature may be due to excessive neural activity associated with chronic pain and inflammation, or from the production of inflammatory mediators which induce vasodilation. Using laser speckle perfusion imaging (LSPI), blood flow to the medial collateral ligament (MCL) of adult rabbits was measured in denervated ACL transected knees (n = 6) and compared to unoperated control (n = 6) and 6-week anterial cruciate ligament (ACL)-transected knees (n = 6). Phenylephrine and neuropeptide Y were applied to the MCL vasculature in topical boluses of 100 microL (dose range 10(-14) to 10(-8) mol and 10(-14) to 10(-9) mol, respectively). Denervation diminished vasoconstrictive responsiveness to phenylephrine compared to both control and ACL-transected knees. Denervation minimally enhanced vascular responses to neuropeptide Y (NPY) compared to ACL deficiency alone, which nevertheless remained significantly diminished from control responses. To evaluate the potential role of inflammatory dilators in the diminished contractile responses, phenylephrine was coadministered with histamine, substance P, and prostaglandin E(2). High-dose histamine, and low-dose substance P and PGE(2) were able to inhibit contractile responses in the MCL of control knees. Excessive neural input does not mediate diminished vasoconstrictive responses in the ACL transected knee; inflammatory mediators may play a role in the deficient vascular responsiveness of the ACL transected knee.
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PMID:Neural stimulation does not mediate attenuated vascular response in ACL-deficient knees: potential role of local inflammatory mediators. 1962 23


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