MEMORY OF ARTERIAL RECEPTOR ACTIVATION INVOLVES REDUCED [CA2-BRIDGES TO [CA2+](I)(](I) AND DESENSITIZATION OF CROSS)

Rabbit femoral arteries retain a memory of previous maximum receptor a ctivation for up to 3-4 h after complete cessation of the stimulus, as reflected by a reduction in the steady-state contraction produced by a subsequent exposure to KCI. The present study examined the hypothesi s that this modulatory effect involves alterations in postreceptor sig nal transduction. To quantify the degree of cellular downregulation in duced by an episode of al-adrenoceptor stimulation, tissues were pretr eated far 30 min with 10(-5) M phenylephrine (PE), washed for 10 min t o cause complete relaxation, and activated with increasing concentrati ons of KCl. Pretreatment of tissues with PE resulted in a large reduct ion compared with control tissues in the ability of 20-60 mM KCl to in crease stress and myosin light-chain phosphorylation. However, only at low (20 and 26 mM), not high (> 26 mM), KCI concentrations did PE pre treatment reduce the ability of KCI to increase intracellular free Ca2 + concentration ([Ca2+](i)). These data support the hypothesis that me mory of receptor activation involves reductions in both Ca2+ mobilizat ion and the sensitivity of contractile proteins to [Ca2+](i).