Effects of oxytocin and methacholine on cyclic nucleotide levels of rabbit myometrium.
The effects of oxytocin and methacholine on cyclic nucleotide levels in estrogen-primed rabbit myometrium were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor. In the absence of MIX, methacholine increased guanosine 3',5'-cyclic monophosphate (cGMP) levels at a time when contraction was decreasing, but had no influence on adenosine 3',5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin did not elevate cGMP, but rapidly decreased cAMP levels. MIX (1 mM) increased both cAMP and cGMP levels. Oxytocin or methacholine further increased cGMP, indicating activation of guanylate cyclase. Oxytocin- but not methacholine-induced stimulation of guanylate  cyclase was abolished in Ca2+-free solution. Oxytocin increased cAMP over the levels produced by MIX alone, whereas methacholine decreased cAMP below the MIX control values; these effects were insensitive to indomethacin. Tissue levels of cGMP and cAMP did not directly correlate with isometric tension. The results also indicate that both oxytocin and methacholine stimulate guanylate cyclase but have opposing effects on adenylate cyclase of rabbit myometrium.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D008688:Methacholine Compounds / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D011817:Rabbits; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
D008688:Methacholine Compounds; D003995:Dibutyryl Cyclic GMP; D010121:Oxytocin; D003994:Bucladesine; D000242:Cyclic AMP; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine