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Characteristics of histamine tachyphylaxis in rat uterine smooth muscle
I Martínez-Mir1, M Gil Marqués, F J Morales-Olivas
1Departament de Farmacologia, Universitat de València, Spain.
Objective And Design:
To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus.
Material:
Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used.
Treatment:
Repetitive responses to histamine (10(-6), 10(-5), 10(-4), 10(-3) M), dimaprit and clonidine (10(-4) M) were tested at 15, 30, 45 and 105 min., with their modifications by (5 mg/kg, 24 h before sacrifice) reserpine, 10(-7) M propranolol, 10(-8) M atropine, and 10(-6) M indomethacin. Dose-response curves for adrenaline were carried out as standard protocol.
Methods:
In vitro techniques (de Jalon's solution, 31 degrees C, carbogen, isotonic registration, resting tension 1 g). Levels of cAMP were studied in response to histamine, adrenaline and isoproterenol by radioassay.
Results:
Repeated histamine produced a rapid loss of inhibitory uterine response depending on the number of exposures and increase in concentration. The tachyphylaxis phenomenon is not modified by the different pretreatments used. Dimaprit, but not clonidine or adrenaline, produced tachyphylaxis. The second exposition to 10(-3) M histamine produced a 38.8% reduction in cAMP production.
Conclusion:
Histamine appears to induce homologous and probably cAMP-dependent desensitisation of H2-receptors.
