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Molecular Pharmacology

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Abstract

Bradykinin analogs antagonize bradykinin-induced second messenger production in a sensory neuron cell line.

P C Francel, J F Keefer and G Dawson
Molecular Pharmacology January 1989, 35 (1) 34-38;
P C Francel
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J F Keefer
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G Dawson
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Abstract

Bradykinin is the prime initiator of pain and the key initial activator of the inflammatory response at the site of tissue injury. The subsequent transfer of nociceptive information (pain sensation) into the central nervous system is then mediated via afferent type C dorsal root ganglion neurons. A recently developed hybrid cell line, F-11, shows many qualities characteristic of these pain-sensitive cells. In these neuronal hybrids, we have found that bradykinin induces sequential elevation in the concentrations of several second messengers involved in neuronal activation, including inositol trisphosphate (6.5-fold), intracellular calcium (2.7-fold), and cyclic GMP (20.5-fold). Importantly, the production of these second messengers is potently inhibited by several novel bradykinin antagonists that possess no intrinsic agonist activity. The same relative rank order of potency of inhibition of bradykinin-induced second messenger production was achieved in the inositol trisphosphate, calcium, and cyclic GMP assay systems, suggesting strongly that all three messenger systems are being activated by the same bradykinin receptor. The most potent antagonist was D-Arg0-Hyp3-Thi5,8-D-Phe7-bradykinin, which inhibited in a competitive manner, with pA2 values, upon Schild plot analysis, in the nanomolar range. These potent bradykinin antagonists may be useful in the characterization of bradykinin receptors and in the clinical management of pain and inflammation.

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Molecular Pharmacology
Vol. 35, Issue 1
1 Jan 1989
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Abstract

Bradykinin analogs antagonize bradykinin-induced second messenger production in a sensory neuron cell line.

P C Francel, J F Keefer and G Dawson
Molecular Pharmacology January 1, 1989, 35 (1) 34-38;

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Abstract

Bradykinin analogs antagonize bradykinin-induced second messenger production in a sensory neuron cell line.

P C Francel, J F Keefer and G Dawson
Molecular Pharmacology January 1, 1989, 35 (1) 34-38;
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