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)

Cisternal blood injection in the rat and squirrel monkey produces a biphasic cerebral vasospasm, a decrease in cerebral blood flow (CBF) and an increase in glucose uptake (CMRglu) due to an anaerobic glucolysis actually representing a decrease in metabolism. Lesioning of the A2-nucleus, its ascending cathecolamine pathways or their projection site, the median eminence in the hypothalamus, prevents the occurrence of spasm. A unilateral postganglionic trigeminal lesion causes an ipsilateral constriction of the cerebral arteries while a preganglionic lesion does not affect the baseline arterial diameter. Both kinds of trigeminal lesions induce a global increase in glucose uptake of about 50% without influencing CBF. Following subarachnoid hemorrhage (SAH) the decrease in CBF in both groups of lesioned animals is similar to that seen in controls. After SAH there is no further change in CMRglu in the animals with a preganglionic lesion, while in the postganglionically lesioned animals there is an additional increase in CMRglu of about 50% as compared to controls or animals with a preganglionic lesion. Treatment with the peptidergic substance P (SP) antagonist, spantide, or gammaglobulin against SP prevents or significantly reduces the degree of spasm and the changes in flow and metabolism normally seen post-SAH. The non-peptidergic neurokinins NK1 and NK3 antagonists do not influence flow and metabolism in SAH animals. The NK2 seems to change both flow and metabolism post-SAH in rats.
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PMID:Trigeminal nerve and brainstem catecholamine systems in cerebral vasospasm. 1023 97

Substance P (SP), a putative sensory neurotransmitter, mediates reflex laryngeal adductor activity in developing dogs. Such reflex activity includes life-threatening laryngospasm induced by stimulation of distal esophageal afferent nerves. The site of SP's activity is unknown. This research was undertaken to determine whether injection of SP into the nucleus tractus solitarius (NTS) of developing beagles alters laryngeal adductor motor activity. Six animals, 57 to 78 days of age, underwent stereotactic injection of 5 to 10 microL of SP into the region of the NTS, identified by electrical stimulation of the ipsilateral superior laryngeal nerve. In 8 additional studies, SP was injected into the cerebellum (2) or brain stem (6) distant from the NTS. Cardiovascular and electromyographic (EMG) responses of the diaphragm and the cricothyroid (CT) and/or thyroarytenoid (TA) muscles were recorded in all 6 animals. Injection of SP into the region of the NTS induced a decrease in blood pressure in all animals and an increase in either ipsilateral CT or TA activity. Three of these animals experienced mixed apnea characterized by sustained EMG activity (spasm) of the ipsilateral CT or TA muscles and an absence of diaphragm EMG activity. The apnea event was fatal in 1 of these animals. In the 6 animals who underwent injections in the brain stem but outside the region of the NTS, diaphragm and laryngeal EMG activity generally did not change after injection of SP, with the exception of 1 animal who experienced a mild, short-lived increase in ipsilateral CT activity. A brief phasic increase in ipsilateral CT activity was seen in both animals who underwent injection of SP into the cerebellum. A putative sensory neurotransmitter, SP evokes ipsilateral CT and/or TA EMG activity when injected into the region of the NTS in developing beagle dogs. This research suggests that SP in the NTS may play a role in mediating life-threatening laryngeal adductor reflexes in developing mammals and may provide important information regarding therapeutic intervention.
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PMID:Response of the cricothyroid and thyroarytenoid muscles to stereotactic injection of substance P into the region of the nucleus tractus solitarius in developing dogs. 1113 Aug 29

Since serotonin (5-HT) is implicated in exacerbating acute coronary syndromes, we studied the reactivity of atrial coronary arterioles (70-140 microm) of atherosclerotic patients undergoing cardiac surgery to 5-HT, substance P (Sub P), and sodium nitroprusside by video-microscopy. Before ischemia, 5-HT-induced relaxation was not affected by NS398 (cyclooxygenase inhibitor), H2O2 or U63557A (thromboxane A2 synthase inhibitor), but was reduced by L-NNA. 5-HT elicited a potent contractile response after ischemia that was inhibited by NS398, Indo, and U63557A. While Sub P relaxation was decreased after ischemia, SNP relaxation was unchanged. The mRNA steady-state levels of NOS-3, NOS-2, prostacyclin synthase, and COX- 1 were not altered by ischemia. COX-2 mRNA and protein levels (Westernblotting), however, were increased (mean +/- SEM) 2.4 +/- 0.4 and 3.2 +/- 0.7 fold, respectively, in ischemic atrium corroborating with the immunohistochemistry of atrial tissue. It is concluded that myocardial ischemia enhanced contractile response of coronary arterioles to 5-HT maybe due to the stimulated prostaglandin release (likely thromboxane A2) secondary to induction of COX-2 expression. These findings may have implications regarding the cause of coronary spasm during acute myocardial ischemia.
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PMID:Serotonin-induced human coronary microvascular contraction during acute myocardial ischemia is blocked by COX-2 inhibition. 1121 33


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