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Evaluation of ICI D7114, a putative stimulant of brown adipocytes, on histamine‐contracted guinea‐pig ileum
Author(s) -
Growcott J.W.,
Wilson Campbell,
Holloway Brian,
Mainwaring Sally
Publication year - 1993
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.1476-5381.1993.tb13751.x
Subject(s) - isoprenaline , endocrinology , medicine , propranolol , histamine , ileum , methysergide , guinea pig , agonist , chemistry , biology , receptor , serotonin , stimulation
1 Experiments were performed to characterize the effects of the novel brown adipocyte stimulant, ICI D7114, in the guinea‐pig isolated ileum, right atrium and tracheal chain. In the ileum, agonist‐induced inhibition of the contractile response to either histamine or prostaglandin E 2 (PGE 2 ) was assessed, along with effects on resting rate in the atrium and resting tone in the tracheal chain. In the latter two preparations, antagonism of isoprenaline‐induced responses by ICI D7114 was also assessed. 2 Inhibitory responses were obtained in the ileum to ICI D7114, isoprenaline, BRL37344, and noradrenaline. The responses to ICI D7114, isoprenaline and BRL37344 were resistant to blockade with propranolol (5 μ m ), naloxone (1 μ m ), methysergide (0.1 μ m ), cimetidine, indomethacin and 8‐phenyltheophylline (all 10 μ m ). These responses to isoprenaline, in the presence of propranolol (5 μ m ), were competitively antagonized by alprenolol (1–100 μ m ) with a pA 2 value of 6.44. The responses to ICI D7114 and BRL37344 were antagonised by single concentrations of alprenolol (1 μ m ) with apparent p K B values of 6.53 and 6.57 respectively. These data indicate an effect of ICI D7114 at the atypical β‐adrenoceptor in the guinea‐pig ileum. 3 The order and relative potency of agonists at the atypical β‐adrenoceptor was BRL37344 (4) > isoprenaline (1) = ICI D7114 (1.1) > noradrenaline (0.5). 4 ICI D7114 (1 n m –10 μ m ) caused no significant change in the rate of beating or the resting tone of the guinea‐pig right atrium or tracheal chain respectively. It did, however, cause selective blockade of the responses to isoprenaline in these tissues (apparent p K B values 7.63 and 5.85 in atrium and tracheal chain respectively). Responses to histamine (atrium) and aminophylline (tracheal chain) were not significantly affected by 10 μ m ICI D7114. 5 These results demonstrate that ICI D7114 possesses selective agonist activity at atypical β‐adrenoceptors in the guinea‐pig ileum and its use as a tool may help to establish a role for the atypical β‐adrenoceptor in the control of gastrointestinal motility.