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)

Changes in intracellular Ca(2+) concentration ([Ca(2+)]i) induced by agonists were simultaneously monitored in rat submandibular acini and ducts using a Ca(2+) imaging system. Substance P (SP) elicited marked increases in [Ca(2+)]i in acini but not in ducts. Carbachol (CCh) increased [Ca(2+)]i in both acini and ducts, but the maximal level was higher in acini than in ducts. In contrast, epinephrine (Epi) also induced an increase in [Ca(2+)]i in acini and ducts, but to a greater extent in ducts than in acini. Isoproterenol (ISO) caused a small but significant increase in [Ca(2+)]i in ducts but not acini. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis using total RNA extracted from highly purified acinar and ductal cells showed that substance P receptor mRNA was present in acini at higher levels than in ducts. In contrast, alpha(1a)-adrenoceptor mRNA was more strongly expressed in ducts than in acini. The muscarinic receptors (M(3) and M(5)) and beta-adrenoceptors (beta(1) and beta(2)) were expressed at equivalent levels in both cell types. These results confirm that acini and ducts exhibit significant differences in agonist-induced Ca(2+) responses. Furthermore, substance P- and epinephrine-induced Ca(2+) responses were consistent with receptor mRNA expression in acini and ducts, but carbachol- and isoproterenol-induced [Ca(2+)]i increases were not.
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PMID:Comparison of agonist-induced Ca2+ responses in rat submandibular acini and ducts. 1584 52

Small intestinal carcinoids (SICs) are the most prevalent gastrointestinal carcinoid and characterized by local invasion metastasis and protean symptomatology. The proliferative and secretory regulation of the cell of origin, the enterochromaffin (EC) cell has not been characterized. The absence of either a pure preparation of normal EC cells or human EC carcinoid cell lines has hindered the development of therapeutic agents. We therefore further characterized the neoplastic SIC cell line, KRJ-I by assessing its secretory (serotonin (5-HT)) and proliferative responses and defining its log growth phase transcriptome. Electron microscopy demonstrated oval, lobulated nuclei and substance P, and 5-HT-positive cytoplasmic vesicles. RT-PCR detected transcripts for chromogranin A (CHGA), VMAT1 (SLC18A1), tryptophan hydroxylase (TPH1), substance P (TAC1), guanylin (GUCA2A), and SERT (SLC6A4). By immunohistochemistry, all cells were positive for CHGA, SERT, VMAT1, and TPH1. Transcriptome analysis (Affymetrix U133 Plus chips) identified somatostatin SSTR2/3, adrenergic alpha1C and beta1, dopamine D2, nicotinic-type cholinergic A5, A6, B1, muscarinic acetylcholine M4, and 5-HT-2A receptors. The presence of transcripts for SSTR1, SSTR2, and SSTR3 receptors was confirmed by RT-PCR and sequencing. Isoproterenol (ISO) resulted in a dose-dependent increase in intracellular cAMP (EC50=340 nM) and 5-HT (EC50=81 nM) which was completely inhibited by the cAMP antagonist 2',5'-dideoxyadenosine (10 microM). Preincubation with a SSTR agonist, lanreotide, inhibited Ip-stimulated 5-HT secretion (IC50=420 nM). Both lanreotide (10 nM) and rapamycin (50 nM) inhibited proliferation (20+/-12 and 35+/-5% respectively) in serum-free medium whereas gefitinib (1 nM-10 microM) inhibited proliferation at micromolar concentrations. KRJ-I is a neoplastic EC cell line that can be used as an in vitro model of SICs as it will allow elucidation and clarification of the secretory and proliferative mechanism(s) of neoplastic EC cells and the molecular signatures that characterize each of these responses.
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PMID:Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin. 1724 79


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