Agonist induced release of intracellular Ca2+ in the rabbit aorta

Abstract

Summary. The effects of hormonal agonists (norepinephrine, angiotensin, and histamine) on 45Ca efflux from the rabbit aorta were studied using a Ca-EGTA buffered efflux medium. Each caused a transient stimulation of efflux rate which probably reflected the release of an intracellular 45Ca store. The size of the stimulation of efflux correlated with the size of the initial rapid phase of contraction. The norepinephrine-sensitive intracellular Ca fraction was estimated to be greater than 21 gmoles/Kg wet tissue weight. This fraction is separate from intracellular Ca which is accumulated during relaxation. Evidence is presented for the lack of cyclic nucleotide involvement in the release of Ca a+, and possible alternative modes of coupling are discussed.The calcium movements which are responsible for norepinephrine (NE) induced contraction of vascular smooth muscle remain uncertain. Earlier studies by Bohr (1963) described the different sensitivity of the early phasic and latter tonic portions of the contractile response to changes in extracellular Ca. The initial rapid increase in tension was augmented in Ca-free solutions, and reduced in higher than normal Ca (10 raM), while the latter slow increase in tension was reduced in Ca-free solutions and increased in the presence of higher Ca. Hinke, Wilson and Burnham (1964), and later Hudgins (1969) andvan Breemen (1969), noted that the NE response was more resistant to Ca removal than was high K induced contraction, and that NE responsiveness returned at lower Ca levels than high K contractions. Since Briggs (1962) had reported that both NE and high K increased Ca influx, Hinke was led to conclude that NE initially utilizes a more tightly bound Ca fraction, probably located on the outside of the plasma membrane. A number of recent studies have concluded that NE activation involves a combination of cellular and extracellular Ca

Effect of calcium and calmodulin antagonists on contractile responses of the human uterine artery

“…The data showed that the response to K but not that to NA was completely inhibited in a medium lacking Ca but containing lanthanum. This observation strongly argues for an intracellular Ca pool which can be liberated by NA, as has previously been shown for arterial smooth muscle (Deth & van Breemen, 1977;Deth & Lynch, 1981;Godfraind & Dieu, 1981;Godfraind et al, 1983). Recent data of Maigaard et al (1985) on myometrial arteries appear to support this view.…”

“…It has been previously shown that drugs inducing a contraction in vascular smooth muscle may, in addition to opening receptor-operated channels release Ca from intracellular stores (Deth & van Breemen, 1977;Deth & Lynch, 1981; Table 1 Inhibition by various drugs of the contractile response induced by noradrenaline (NA) and high potassium…”

Effects of calcium entry blockers on calcium‐dependent contractions of rat portal vein

“…The presence of an internal calcium store that can be released by various drugs has been demonstrated previously in vascular smooth muscles (Deth & Van Breemen, 1977;Droogmans et al, 1977;Casteels & Droogmans, 1981). This was usually shown by washing the preparation in a Ca2"-free, EGTA-containing solution and inducing a contraction in response to a supra-maximal concentration of drug.…”

Inhibition of calcium channels by harmaline and other harmala alkaloids in vascular and intestinal smooth muscles

“…During these contractions, 45Ca2+ uptake of the muscle increased and harmaline inhibited the increase in 45Ca2+ uptake in these smooth muscles. It has been suggested that sustained contractions in smooth muscle is largely dependent on the influx of external Ca2+ (Cauvin et al, 1983;Karaki & Weiss, 1984), and only initial transient contractions induced by noradrenaline in rabbit aorta (Deth & van Breemen, 1977; and by carbachol in guinea-pig taenia (Ohashi et al, 1974;Brading & Sneddon, 1980) are attributable to release of cellular Ca2 . Inhibition by harmaline of sustained contraction and associated 45Ca2" influx suggest that harmaline inhibits the pathways of Ca2+ influx which are activated by high K+ and receptor agonists.…”