Characteristics of histamine tachyphylaxis in rat uterine smooth muscle.
OBJECTIVE
To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus.


METHODS
Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used.


METHODS
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.


CONCLUSIONS
Histamine appears to induce homologous and probably cAMP-dependent desensitisation of H2-receptors.
Martínez-Mir
I
I
Departament de Farmacologia, Universitat de València, Spain.
Gil Marqués
M
M
Morales-Olivas
F J
FJ
Rubio-Gomis
E
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017259:Dimaprit / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007551:Isotonic Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013618:Tachyphylaxis / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D004967:Estrogens; D017442:Histamine Agonists; D006632:Histamine; D000242:Cyclic AMP; D003000:Clonidine; D004837:Epinephrine; D017259:Dimaprit