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Selective enhancement of histamine H 1 ‐receptor responses in guinea‐pig ileal smooth muscle by 1,4‐dithiothreitol
Author(s) -
Donaldson J.,
Hill S.J.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10171.x
Subject(s) - dithiothreitol , histamine , agonist , chemistry , long term potentiation , dimaprit , medicine , endocrinology , diamine oxidase , receptor , histamine h1 receptor , biochemistry , biology , antagonist , enzyme
1 1,4‐Dithiothreitol (DTT; 1 mM, 30 min preincubation) produced a small, non‐specific potentiation of spasmogenic activity in longitudinal muscle strips of guinea‐pig small intestine. 2 A direct comparison of contractile responses elicited by histamine and a range of H 1 ‐ and non‐H 1 ‐receptor agonists indicated that DTT produced a significantly greater potentiation of H 1 ‐receptor responses. 3 This apparently selective increase in tissue sensitivity to histamine H 1 ‐preceptor agonists did not appear to be a consequence of the inhibition of histamine N‐methyl transferase or diamine oxidase activity. Potentiation of the responses to histamine by DTT was still observed in the presence of SKF 91488 (10 μM) and aminoguanidine (1 μM). 4 The potentiation elicited by DTT was readily reversed by the sulphydryl oxidizing agent dithiobis‐(2‐nitrobenzoic acid) (DTNB). This suggests that the mechanism of action of DTT involves the reduction of disulphide bonds. 5 Exposure of ileal smooth muscle to DTT following desensitization with histamine (100 × EC 50 [‐ DTT]) resulted in a 6.9 ± 0.7 fold shift of the concentration‐response curve to lower agonist concentrations. Conversely, following potentiation of the response to histamine with DTT, exposure of the tissue to desensitizing concentrations of histamine resulted in a dextral shift of the dose‐response curve (dose ratio = 39.5 ± 1.2) to higher agonist concentrations. 6 The results of this study suggest that DTT may be a useful tool with which to investigate histamine H 1 ‐receptor mechanisms in ileal smooth muscle.