title: Dependence of Ca(2+) sensitivity of arterial contractions on history of receptor activation.
abstract: Stimulation of receptors causing arterial contraction may also cause attenuation of cell responsiveness to stimuli. This study tested the hypothesis that attenuation of receptor-induced contractions involves Ca(2+) desensitization. Renal artery rings were pretreated with 10 microM phenylephrine (PE), relaxed with PE washout (plus phentolamine), and then activated by histamine (HA). Pretreatment for 30 min resulted in a rightward shift in the concentration-contraction curve to HA by approximately 1/2 log without a reduction in the slope or maximum response. For example, control and PE-pretreated tissues responded to 0.56 microM HA with strong (0.95 F/F(o)) and weak (0.16 F/F(o)) contractions, respectively, where F/F(o) represents contractile force. This reduced reactivity was completely reversed within 90 min. In fura-loaded tissues, PE pretreatment caused less of a rightward shift in the HA concentration-intracellular free Ca(2+) concentration ([Ca(2+)](i)) curve than in the HA concentration-contraction curve. A dissociation between force and [Ca(2+)](i) was also produced when KCl was used instead of HA. These data suggest that the reduced reactivity produced by PE pretreatment involved, in part, a reduction in the ability of HA to increase the Ca(2+) sensitivity of contractions. These data support the hypothesis that the degree of stimulus-induced Ca(2+) sensitization of contractions is dependent on the history of receptor activation.
authors.affiliation: Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Ratz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology*; D012077:Renal Artery / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D011956:Receptors, Cell Surface; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D006632:Histamine; D002118:Calcium