MEMORY OF PREVIOUS RECEPTOR ACTIVATION INDUCES A DELAY IN CA2+ MOBILIZATION AND DECREASES THE [CA2+](I) SENSITIVITY OF ARTERIAL CONTRACTIONS

alpha(1)-Adrenoceptor agonists not only contract rabbit femoral arteri es, but also desensitize them so that the strength of subsequent contr actions induced by 110 mM KCl is reduced. To determine the mechanisms by which this postreceptor desensitization occurs, tissues loaded with fura-2/AM were pretreated with phenylephrine (PE), washed, then activ ated with submaximum (23 mM) and maximum (30 mM) KCl concentrations. P retreatment of tissues with 1 mu M PE for 1-30 min resulted in reducti ons compared to control in the ability of 30 mM KCl to increase stress (force/tissue cross-sectional area). Pretreatment durations of 20 or 30 min with 10 mu M PE also introduced delays between addition of KCl and commencement of both contraction (9.8 +/- 0.8 and 2.4 +/- 1.4 min when stimulated with, respectively, 23 and 30 mM KCl) and an increase in [Ca2+](i). At the end of the delay period, both [Ca2+](i) and stres s spontaneously increased, but although [Ca2+](i) increased to control levels, stress did not. These data support the hypothesis that at lea st two postreceptor desensitizing mechanisms are activated by prior al pha(1)-adrenoceptor stimulation: (1) short-term inhibition of stimulus -induced increases in [Ca2+](i) and (2) reductions in the sensitivity of the contractile response to [Ca2+](i). Interestingly, caffeine pret reatment mimicked the actions of PE pretreatment, implying that the su perficial buffer barrier function of the sarcoplasmic reticulum or inc reases in cyclic nucleotide levels may have played a role in memory of alpha-adrenoceptor activation in rabbit femoral arteries.