Functional roles of cyclic guanosine 3',5'-monophosphate analogue in cerebral vasodilation.
1. Vasodilating effects of cyclic nucleotides in cerebral vasculature were examined using membrane permeable cyclic nucleotide analogues, 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). 2. In isolated canine basilar artery (CBA), 8-Br-cGMP but not 8-Br-cAMP, significantly inhibited Ca(2+)-induced and agonist [serotonin(5-HT), prostaglandin(PG)F2 alpha or endothelin]-induced contraction, in a concentration-dependent manner. 3. When Ca2+ was depleted from intracellular store sites by pretreatment with A23187, 8-Br-cGMP but not 8-Br-cAMP strongly attenuated contractions induced by Ca(2+)-influx. 4. Neither 8-Br-cGMP nor 8-Br-cAMP modified contraction induced by caffeine which elicits Ca2+ release from intracellular Ca2+ store. 5. 8-Br-cGMP lowered the high K(+)-induced sustained [Ca2+]i elevation. 6. These results suggest that, at least in CBA, cGMP exerts its inhibitory effect on the contraction induced by influx of Ca2+, by reducing the level of [Ca2+]i and reducing [Ca2+]i sensitivity of the contractile machinery.
Exploratory Research Laboratories, Chugai Pharmaceutical Company Ltd, Shizuoka, Japan.
M
M
Sugawa
K
K
Tamura
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T
Koide
S
S
Naitoh
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D014662:Vasoconstrictor Agents; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D000001:Calcimycin; D002110:Caffeine; D006152:Cyclic GMP; D002122:Calcium Chloride; D011188:Potassium; D002118:Calcium