Relaxation by calcitonin gene-related peptide may involve activation of K+ channels in the human uterine artery.
The vasodilatory role of calcitonin gene-related peptide in activating K+ channels was examined in isolated, suffused human uterine arteries. Calcitonin gene-related peptide produced a concentration-dependent relaxation of norepinephrine (1 microM)-induced contractions. Calcitonin gene-related peptide was antagonized by glybenclamide (1-100 microM), an inhibitor of ATP-sensitive K+ channels, but not by tetraethylammonium (1 mM), an inhibitor of calcium(2+)-activated K+ channels. Glybenclamide (10 microM) produced a 6.7 fold and an 11-fold shift to the right of calcitonin gene-related peptide (0.1 to 100 nM) in uterine arteries from pregnant patients (n = 3) and nonpregnant patients (n = 6), respectively. Calcitonin gene-related peptide (10 nM) less effectively (P < 0.05) relaxed contractions produced by KCl (50 mM) (29.4 +/- 1.6%) than by norepinephrine and glybenclamide (10 microM) did not reverse this relaxation (22.2 +/- 6.8%, n = 4 nonpregnant patients). Pinacidil (1 microM), an ATP-sensitive K+ channel opener, relaxed norepinephrine-induced contractions of uterine arteries. Glybenclamide (10 microM) also antagonized pinacidil. These results suggest that calcitonin gene-related peptide relaxes norepinephrine-contracted human uterine arteries, at least in part, by activation of a K+ channel, perhaps of the ATP-sensitive type.
Nelson
S H
SH
Department of Anesthesiology, University of Tas Medical Branch, Galveston, TX 77555-0749.
Suresh
M S
MS
Dehring
D J
DJ
Johnson
R L
RL
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000328:Adult; D001158:Arteries / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020110:Pinacidil; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011247:Pregnancy; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply*; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019789:Tetraethylammonium; D020110:Pinacidil; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide; D005905:Glyburide