5-Hydroxytryptamine1-like receptors linked to increases in intracellular calcium concentration and inhibition of cyclic AMP accumulation in cultured vascular smooth muscle cells derived from bovine basilar artery.
Vascular smooth muscle cells derived from bovine basilar artery by the explant method were grown in culture. In the presence of 1 microM forskolin and the phosphodiesterase inhibitor rolipram, 5-hydroxytryptamine (5-HT) agonists inhibited by 90 to 100% the accumulation of intracellular cyclic AMP (cAMP) with a rank order of potency 5-carboxamidotryptamine (5-CT) > or = 5-HT > 5-benzyloxytryptamine = sumatriptan > RU24969 [5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate] > (+/-)-8-hydroxydipropylaminotetralin. In suspensions of cells loaded with the calcium-sensitive probe fura-2, 5-CT and 5-HT caused a biphasic increase in the concentration of intracellular free calcium ([Ca++]i) that consisted of both transient and sustained phases. The transient phase was reduced and the sustained phase abolished in the absence of extracellular calcium. The EC50 for 5-CT-induced increase in [Ca++]i (6 nM) was similar to that for inhibition of cAMP accumulation (1.3 nM). Both the inhibition of cAMP accumulation and increase in [Ca++]i were inhibited by the antagonist methiothepin (pA2 = 8.9), but not by the antagonists ketanserin, spiperone and pindolol. Both the inhibition of cAMP accumulation and increase in [Ca++]i were attenuated by greater than 85% in cells that were pretreated with pertussis toxin. PI turnover was not stimulated by 5-CT. The rank order of agonist potency, as well as the antagonist sensitivity, indicates responses mediated by one or more 5-HT1-like-type receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesiology, Mount Sinai School of Medicine, New York, New York.
B J
BJ
Ebersole
C A
CA
Diglio
D W
DW
Kaufman
K A
KA
Berg
D000818:Animals; D001488:Basilar Artery / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D037342:Pertussis Toxin; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D010566:Virulence Factors, Bordetella; D012701:Serotonin; C047087:5-carboxamidotryptamine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D002118:Calcium