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 arteries, but also desensitize them so that the strength of subsequent contractions 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 activated with submaximum (23 mM) and maximum (30 mM) KCl concentrations. Pretreatment of tissues with 1 microM PE for 1-30 min resulted in reductions 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 microM 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 stress spontaneously increased, but although [Ca2+]i increased to control levels, stress did not. These data support the hypothesis that at least two postreceptor desensitizing mechanisms are activated by prior alpha 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 pretreatment mimicked the actions of PE pretreatment, implying that the superficial buffer barrier function of the sarcoplasmic reticulum or increases in cyclic nucleotide levels may have played a role in memory of alpha-adrenoceptor activation in rabbit femoral arteries.
Ratz
P H
PH
Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501, USA.
Salomonsky
P M
PM
Lattanzio
F A
FA
D000818:Animals; D001158:Arteries / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D010656:Phenylephrine; D002110:Caffeine; D011189:Potassium Chloride; D002118:Calcium