Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A permanent line of cells has been established from the transplantable rat pituitary tumor 7315a. P11 cells have been cloned repeatedly, and after more than 60 passages their growth and characteristics are stable. Results of radioligand binding studies with 125I-lysergic acid diethylamide (125I-LSD) indicate that P11 cells express serotonin-2 (5-HT2) receptors. Analysis of the binding of 125I-LSD to membranes prepared from P11 cells revealed the presence of a single class of high affinity sites (Kd = 1.6 nM; Bmax = 211 fmol/mg of protein). The pharmacological profile of the inhibition of the binding of 125I-LSD by a panel of drugs was consistent with the expected profile of these drugs at 5-HT2 receptors. The affinity of the site for serotonin was in the low micromolar range and was decreased by GTP. Phosphoinositide hydrolysis in P11 cells, measured in the presence of lithium, was stimulated by serotonin. Increasing concentrations of the 5-HT2-selective antagonist ketanserin blocked phosphoinositide hydrolysis stimulated by serotonin, and Schild analysis was consistent with a simple competitive interaction. The Ki for ketanserin derived from Schild analysis was comparable to the Ki for ketanserin at the binding site for 125I-LSD. These results suggest that stimulation of phosphoinositide hydrolysis in P11 cells by serotonin is mediated by 5-HT2 receptors. Pretreatment of P11 cells with pertussis toxin caused ADP-ribosylation of Gi and Go, but did not affect the ability of serotonin to stimulate phosphoinositide hydrolysis. Therefore, the guaninine nucleotide-binding protein involved in the coupling of 5-HT2 receptors to phospholipase C in P11 cells is unlikely to be either Gi or Go. P11 cells expressing 5-HT2 receptors coupled to phosphoinositide hydrolysis will be a useful model system for future studies of the regulation and function of 5-HT2 receptors on cultured cells.
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PMID:Serotonin-2 receptors coupled to phosphoinositide hydrolysis in a clonal cell line. 216 57

To examine the role of guanine nucleotide binding (G) proteins in receptor-mediated inhibition of serotonin (5-HT) neurons, we intracerebrally injected pertussis toxin (0.5-1.0 microgram) into rat midbrain in a region immediately rostral to the dorsal raphe nucleus. The baseline firing rate of extracellularly recorded 5-HT neurons was not significantly affected by pertussis toxin treatment. However, in comparison to saline-injected controls, pertussis toxin-injected animals showed markedly blunted sensitivity to agonists that act at 5-HT autoreceptors (isapirone, 5-HT and LSD) and to baclofen, a GABAB agonist. This pertussis toxin-induced blunting of sensitivity was demonstrated in vivo (with intravenous and iontophoretic application of drugs) and in vitro in the dorsal raphe brain slice preparation. The sensitivity of iontophoretically applied GABA itself was not significantly decreased with pertussis toxin treatment, consistent with evidence that GABA administered in this manner acts on dorsal raphe cells mainly through GABAA receptors. Our data provide strong evidence for the role of a pertussis toxin substrate(s) (presumably a G protein(s] in mediating the inhibition induced by the autoreceptor and GABAB receptor on 5-HT neurons in rat dorsal raphe nucleus.
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PMID:Pertussis toxin blocks 5-HT1A and GABAB receptor-mediated inhibition of serotonergic neurons. 282 89

The G protein coupling of human 5-hydroxytryptamine5A (h5-ht5A) receptors was investigated in stably transfected human embryonic kidney (HEK) 293 cells, using radioligand and guanosine-5'[gamma-35S]thiotriphosphate binding to membranes and cyclic adenosine monophosphate measurements in cells. 5-Carboxamido[3H]tryptamine bound to high- and low-affinity sites on h5-ht5A-HEK 293 cell membranes. Guanylyl-imidodiphosphate addition and pertussis toxin pre-treatment abolished high-affinity binding, indicating coupling to G proteins of the Gi/Go family. [N-methyl-3H]Lysergic acid diethylamide bound to a single site; guanylyl-imidodiphosphate and pertussis toxin did not alter lysergic acid diethylamide affinity. 5-Hydroxytryptamine stimulated guanosine-5'[gamma-35S]thiotriphosphate binding to 130% over basal and this effect was completely abolished by pertussis toxin. Various 5-hydroxytryptamine receptor ligands were tested for inhibition of 5-carboxamido[3H]tryptamine binding and in guanosine-5'[gamma-35S]thiotriphosphate binding assays. 5-Hydroxytryptamine consistently inhibited forskolin-induced cyclic adenosine monophosphate formation by 25% in h5-ht5A-HEK 293 cells; no effect was detected on basal cyclic adenosine monophosphate levels, on intracellular Ca2+ concentration or arachidonic acid release. Our studies demonstrate functional coupling of the h5-ht5A receptor to pertussis toxin-sensitive G proteins and to inhibition of adenylate cyclase activity.
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PMID:The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells. 986 21

The guinea pig 5-hydroxytryptamine(5A) (gp5-ht(5A)) receptor was cloned from guinea pig brain using degenerate polymerase chain reaction (PCR) and shows 88%, 85% and 84% amino acid sequence identity versus the human, rat and mouse 5-ht(5A) receptors, respectively. The receptor was transiently expressed in human embryonic kidney (HEK) 293 cells. [(3)H]-Lysergic acid diethylamide (LSD) bound saturably to gp5-ht(5A)/HEK293 membranes with a K(d) of 2.3+/-0.1 nM and B(max) of 15.7+/-3.4 pmol/mg protein. The receptor binding profile, determined by competition with [(3)H]LSD, correlated well with that for the human 5-ht(5A) receptor. 5-HT stimulated [(35)S]GTPgammaS binding to gp5-ht(5A)/HEK293 membranes (pEC(50) 8.1+/-0.2), and the response was surmountably antagonised by methiothepin and ritanserin, giving apparent pK(B) values of 8.0 and 7.2, respectively. The 5-HT response was absent using membranes prepared from gp5-ht(5A)/HEK293 cells pretreated with pertussis toxin (PTX). These data suggest that the gp5-ht(5A) receptor couples to G(i)-proteins in this expression system and shows a similar pharmacological profile to that for the human 5-ht(5A) receptor.
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PMID:Cloning and pharmacological characterisation of the guinea pig 5-ht5A receptor. 1521 62