Investigation of the Role of Calcium in the Super‐sensitivityproduced by Cocaine in Cat Spleen Strips

Abstract

Cocaine (2 × 10−6m and 10−5m) produced 2 and 7 fold shifts to the left of the dose‐response curve to (—)‐noradrenaline recorded isotonically in isolated splenic capsular strips of the cat. The same concentrations of cocaine also produced increases in the maximum response of the tissue to 117% and 126.7% of control. Desmethylimipramine (DMI, 10 −7 to 10−6m) produced no significant potentiation of the response of cat spleen strips to (—)‐noradrenaline. At 10−5 M DMI decreased the maximum response. Cocaine (10−5m) produced a 3.3 fold shift to the left of the dose‐response curve whereas DMI (10−6m) had no effect on the dose‐response curve to oxymetazoline in cat splenic capsular strips. Cocaine (10−5m) in the presence of phentolamine (10−6m) produced a shift to the left and an increase in the maximum response to K+, an agonist which is believed to produce muscle contraction by increasing the membrane calcium flux. Cocaine (10−5m) had no effect on the dose‐response curve to angiotensin which is believed to contract vascular muscle by releasing calcium from intracellular storage sites. The potentiating effect of cocaine (10−5m) on responses of spleen strips to (—)‐noradrenaline was blocked by the calcium flux inhibitor SKF 525A (2.65 × 10−5m). It is concluded that the results are compatible with the view that cocaine enhances the influx of calcium across the cell membrane during responses to agonists that utilize the extracellular pool of calcium and that this effect is responsible for a large part of the potentiation of the response.

Cocaine-calcium channel antagonist interactions

“…In rats concurrently given nitrendipine, heart rate increased only by 40%, no tachyarrhythmias or convulsions were seen, and the LDso increased to 618 mg/kg. In isolated cat spleen strips, potentiation of norepinephrine effects by cocaine was reversed by calcium channel antagonists (Summers and Tillman 1979). The authors hypothesized that one action of cocaine is increased calcium flux across cell membranes.…”

Cocaine Use and Splenic Rupture: A Rare Yet Serious Association

“…First is the direct vasoconstrictive effect mediated via increased influx of calcium across the vascular endothelium as has been proven in animal studies. 8 The other is vasospasm and poor blood flow in the mucosal vessels due to the sympathomimetic effects of cocaine in the gut vasculature. Apart from vasoconstriction, cocaine can cause ischemia by promoting intramural thrombus formation.…”

Effects of cocaine on Ca-mobility in microsomal fraction from rat vas deferens.

“…Cocaine has been reported to potentiate the maximal response in several organs, such as rat vas deferens (2,5) and cat spleen (3,4,17). Many investigations have indi cated that cocaine has not only an inhibitory action on catecholamine uptake mechanism, but also a stimulating action on smooth muscle cells.…”

“…Summers and Tillman (17) observed that in cat spleen, cocaine potentiation was diminished in the presence of SKF525A, a potent calcium influx inhibitor, although the sources of Ca' to be utilized for contraction in this organ were controversial. Their finding suggested that Ca-influx induced by smooth muscle stimulants increased in the presence rather than in the absence of cocaine.…”