Inhibition of human polymorphonuclear leukocyte-derived histaminase activity by H-2 antagonists

Larry L. Thomas; Bruce S. Bochner; Lawrence M. Lichtenstein

doi:10.1016/0006-2952(78)90327-1

Inhibition of human polymorphonuclear leukocyte-derived histaminase activity by H-2 antagonists

Larry L. Thomas^*, Bruce S. Bochner, Lawrence M. Lichtenstein

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

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Original language	English (US)
Pages (from-to)	2562-2565
Number of pages	4
Journal	Biochemical Pharmacology
Volume	27
Issue number	21
DOIs	https://doi.org/10.1016/0006-2952(78)90327-1
State	Published - 1978

ASJC Scopus subject areas

Biochemistry
Pharmacology

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10.1016/0006-2952(78)90327-1

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@article{4f22686a70d0444ab7b58fd620459dba,

title = "Inhibition of human polymorphonuclear leukocyte-derived histaminase activity by H-2 antagonists",

author = "Thomas, {Larry L.} and Bochner, {Bruce S.} and Lichtenstein, {Lawrence M.}",

note = "Funding Information: To obtain histaminase, human polymorphonuclear Histaminase activity was linear with time for IS hr of leukocytes were isolated from venous blood of a normal incubation (Fig. 1, left panel). Activity was completely donor by Hypaque-Ficoll density centrifugation [13]. abolished by 10-j M aminoguanidine, a specific inhibitor Contaminating erythrocytes were removed by hypotonic of diamine oxidase 1141. A Lineweaver-Burk plot of Iysis and the PMN suspended at lo7 cells/ml in a 0.025M activity vs substrate concentration yielded a Km of Tris buffer, pH 7.4, containing 0.3 m&ml of human 2.4 x lo-” M (Fig. 1, right panel). This value agrees with serum albumin, 0.6 mM CaCI,, and 1 mM MgQ the K, of 2.5 x lo-” M reported by Zeiger et al. [3] for (TACM) [I]. One-ml volumes of the PMN suspension histaminase activity of human PMN lysates. It also were incubated with 5 pgfml of A23187 (suspended in corresponds closely to the K,,, of 2.8 x 10-O M obtained buffer) for 30 min at 37”. Zeiger et al. [3] demonstrated for histaminase purified from human placenta [IS]. that A23187 releases all of the intra~llul~ histaminase Sig~ficant i~ibition of histaminase activity was activity within 30 min and this has been confirmed in our observed with each of the three H-2 antagonists at laboratory. Incubations were stopped by a Zmin centri-concentrations of IV M and greater (Fig. 2). Burimam-fugation at 1OOOgand the cell-free supernatant fractions ide was particularly potent, c&sing complere inhibition were pooled. The pooled supernatant fraction was diluted at 1O-5 M. In contrast, diphenhydramine, an H-l antag-1 : 1 with buffer to yield activity derived from 5 x lo6 onist, possessed minimal inhibitory activity; pyrilamine, PMN/ml and divided into aliquots for storage at - 20”. chlorpheniramine and cyclizine were similarly without Histaminase activity was measured by the method of etiect. Of the H-l antagonists examined, only prometha-zine produced significant inhibition (50 per cent at lo-” M * Publication No. 316 from the O{\textquoteright}Neill Research but none at lO-SM). Thus, with the possible exception of Laboratories. The Good Samaritan Hospital, 5601 Loch the oh~nothiaziIle class. the i~ibition was specific for the Raven Blvd, Baltimore, MD 21239. This. work was H-2-antagonists. The{\textquoteright} inhibition by phenothiazines is supported in part by National Institutes of Health being pursued further. A similar pattern of inhibition was Grant AI 11334. obtained for H-2 antagonists with histaminase prepared 2562 Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

year = "1978",

doi = "10.1016/0006-2952(78)90327-1",

language = "English (US)",

volume = "27",

pages = "2562--2565",

journal = "Biochemical Pharmacology",

issn = "0006-2952",

publisher = "Elsevier Inc.",

number = "21",

}

TY - JOUR

T1 - Inhibition of human polymorphonuclear leukocyte-derived histaminase activity by H-2 antagonists

AU - Thomas, Larry L.

AU - Bochner, Bruce S.

AU - Lichtenstein, Lawrence M.

N1 - Funding Information: To obtain histaminase, human polymorphonuclear Histaminase activity was linear with time for IS hr of leukocytes were isolated from venous blood of a normal incubation (Fig. 1, left panel). Activity was completely donor by Hypaque-Ficoll density centrifugation [13]. abolished by 10-j M aminoguanidine, a specific inhibitor Contaminating erythrocytes were removed by hypotonic of diamine oxidase 1141. A Lineweaver-Burk plot of Iysis and the PMN suspended at lo7 cells/ml in a 0.025M activity vs substrate concentration yielded a Km of Tris buffer, pH 7.4, containing 0.3 m&ml of human 2.4 x lo-” M (Fig. 1, right panel). This value agrees with serum albumin, 0.6 mM CaCI,, and 1 mM MgQ the K, of 2.5 x lo-” M reported by Zeiger et al. [3] for (TACM) [I]. One-ml volumes of the PMN suspension histaminase activity of human PMN lysates. It also were incubated with 5 pgfml of A23187 (suspended in corresponds closely to the K,,, of 2.8 x 10-O M obtained buffer) for 30 min at 37”. Zeiger et al. [3] demonstrated for histaminase purified from human placenta [IS]. that A23187 releases all of the intra~llul~ histaminase Sig~ficant i~ibition of histaminase activity was activity within 30 min and this has been confirmed in our observed with each of the three H-2 antagonists at laboratory. Incubations were stopped by a Zmin centri-concentrations of IV M and greater (Fig. 2). Burimam-fugation at 1OOOgand the cell-free supernatant fractions ide was particularly potent, c&sing complere inhibition were pooled. The pooled supernatant fraction was diluted at 1O-5 M. In contrast, diphenhydramine, an H-l antag-1 : 1 with buffer to yield activity derived from 5 x lo6 onist, possessed minimal inhibitory activity; pyrilamine, PMN/ml and divided into aliquots for storage at - 20”. chlorpheniramine and cyclizine were similarly without Histaminase activity was measured by the method of etiect. Of the H-l antagonists examined, only prometha-zine produced significant inhibition (50 per cent at lo-” M * Publication No. 316 from the O’Neill Research but none at lO-SM). Thus, with the possible exception of Laboratories. The Good Samaritan Hospital, 5601 Loch the oh~nothiaziIle class. the i~ibition was specific for the Raven Blvd, Baltimore, MD 21239. This. work was H-2-antagonists. The’ inhibition by phenothiazines is supported in part by National Institutes of Health being pursued further. A similar pattern of inhibition was Grant AI 11334. obtained for H-2 antagonists with histaminase prepared 2562 Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 1978

Y1 - 1978

UR - http://www.scopus.com/inward/record.url?scp=0018087364&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018087364&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(78)90327-1

DO - 10.1016/0006-2952(78)90327-1

M3 - Article

C2 - 31886

AN - SCOPUS:0018087364

VL - 27

SP - 2562

EP - 2565

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 21

ER -

Inhibition of human polymorphonuclear leukocyte-derived histaminase activity by H-2 antagonists

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