Monocytes express a non-neurokinin substance P receptor that is functionally coupled to MAP kinase

Authors: Jeurissen, F., Kavelaars, A., Korstjens, M., Broeke, D., Franklin, R.A., Gelfand, E.W. and Heijnen, C.J.

Journal: Journal of Immunology

Volume: 152

Issue: 6

Pages: 2987-2994

ISSN: 0022-1767

Abstract:

The data presented in this paper demonstrate a new substance P (SP) binding site that is expressed on human monocytes. The apparent dissociation constant (K(d)) for binding of 125I-labeled Bolton Hunter-SP (125I-BH- SP) to the receptor on monocyte membranes is 2.24 ± 0.9 x 10-7 M and the maximum binding capacity (B(max)) is 4.7 ± 0.5 pmol/mg membrane protein. It could be excluded that this receptor is one of the known neurokinin (NK) type of receptors on the basis of binding characteristics for NK1, NK2, and NK3 agonists. Moreover, we demonstrate that the binding site is neither the bombesin receptor nor the serpin enzyme complex receptor nor the FMLP receptor. The order of potency for inhibition of 125I-BH-SP binding to the receptor on monocyte membranes is NK1 antagonist [D-Pro2,D-Trp7,9]SP > SP > NK3 agonist [MePhe7]SP > bombesin. Cross-linking studies with disuccinimidylsuberate, followed by SDS-PAGE analysis, revealed that 125I- BH-SP is specifically bound to a membrane protein with an apparent molecular mass of 47 kDa. At a functional level, SP induces the activation of MAP kinase in human monocytes. The ED50 for activation of MAP kinase positively correlated (r = 0.999, p < 0.0005) with the apparent affinity of the ligands applied in the 125I-BH-SP displacement studies. From these results, we conclude that this SP binding site on monocytes is a non-NK receptor protein that is functionally linked to the activation of MAP kinase.

Source: Scopus

Monocytes express a non-neurokinin substance P receptor that is functionally coupled to MAP kinase.

Authors: Jeurissen, F., Kavelaars, A., Korstjens, M., Broeke, D., Franklin, R.A., Gelfand, E.W. and Heijnen, C.J.

Journal: J Immunol

Volume: 152

Issue: 6

Pages: 2987-2994

ISSN: 0022-1767

Abstract:

The data presented in this paper demonstrate a new substance P (SP) binding site that is expressed on human monocytes. The apparent dissociation constant (Kd) for binding of 125I-labeled Bolton Hunter-SP (125I-BH-SP) to the receptor on monocyte membranes is 2.24 +/- 0.9 x 10(-7) M and the maximum binding capacity (Bmax) is 4.7 +/- 0.5 pmol/mg membrane protein. It could be excluded that this receptor is one of the known neurokinin (NK) type of receptors on the basis of binding characteristics for NK1, NK2, and NK3 agonists. Moreover, we demonstrate that the binding site is neither the bombesin receptor nor the serpin enzyme complex receptor nor the FMLP receptor. The order of potency for inhibition of 125I-BH-SP binding to the receptor on monocyte membranes is NK1 antagonist [D-Pro2,D-Trp7,9]SP > SP > NK3 agonist [MePhe7]SP > bombesin. Cross-linking studies with disuccinimidylsuberate, followed by SDS-PAGE analysis, revealed that 125I-BH-SP is specifically bound to a membrane protein with an apparent molecular mass of 47 kDa. At a functional level, SP induces the activation of MAP kinase in human monocytes. The ED50 for activation of MAP kinase positively correlated (r = 0.999, p < 0.0005) with the apparent affinity of the ligands applied in the 125I-BH-SP displacement studies. From these results, we conclude that this SP binding site on monocytes is a non-NK receptor protein that is functionally linked to the activation of MAP kinase.

Source: PubMed

MONOCYTES EXPRESS A NON-NEUROKININ SUBSTANCE-P RECEPTOR THAT IS FUNCTIONALLY COUPLED TO MAP KINASE

Authors: JEURISSEN, F., KAVELAARS, A., KORSTJENS, M., BROEKE, D., FRANKLIN, R.A., GELFAND, E.W. and HEIJNEN, C.J.

Journal: JOURNAL OF IMMUNOLOGY

Volume: 152

Issue: 6

Pages: 2987-2994

eISSN: 1550-6606

ISSN: 0022-1767

Source: Web of Science (Lite)

Monocytes express a non-neurokinin substance P receptor that is functionally coupled to MAP kinase.

Authors: Jeurissen, F., Kavelaars, A., Korstjens, M., Broeke, D., Franklin, R.A., Gelfand, E.W. and Heijnen, C.J.

Journal: Journal of immunology (Baltimore, Md. : 1950)

Volume: 152

Issue: 6

Pages: 2987-2994

eISSN: 1550-6606

ISSN: 0022-1767

Abstract:

The data presented in this paper demonstrate a new substance P (SP) binding site that is expressed on human monocytes. The apparent dissociation constant (Kd) for binding of 125I-labeled Bolton Hunter-SP (125I-BH-SP) to the receptor on monocyte membranes is 2.24 +/- 0.9 x 10(-7) M and the maximum binding capacity (Bmax) is 4.7 +/- 0.5 pmol/mg membrane protein. It could be excluded that this receptor is one of the known neurokinin (NK) type of receptors on the basis of binding characteristics for NK1, NK2, and NK3 agonists. Moreover, we demonstrate that the binding site is neither the bombesin receptor nor the serpin enzyme complex receptor nor the FMLP receptor. The order of potency for inhibition of 125I-BH-SP binding to the receptor on monocyte membranes is NK1 antagonist [D-Pro2,D-Trp7,9]SP > SP > NK3 agonist [MePhe7]SP > bombesin. Cross-linking studies with disuccinimidylsuberate, followed by SDS-PAGE analysis, revealed that 125I-BH-SP is specifically bound to a membrane protein with an apparent molecular mass of 47 kDa. At a functional level, SP induces the activation of MAP kinase in human monocytes. The ED50 for activation of MAP kinase positively correlated (r = 0.999, p < 0.0005) with the apparent affinity of the ligands applied in the 125I-BH-SP displacement studies. From these results, we conclude that this SP binding site on monocytes is a non-NK receptor protein that is functionally linked to the activation of MAP kinase.

Source: Europe PubMed Central