Systemic choline is a moderately effective analgesic via activation of alpha7 nicotinic acetylcholine receptors. The antinocicepive effect may not be mediated by a reduction of TNF pathway cytokine release from macrophages. Although choline at millimolar concentrations clearly inhibits the release of TNF, this effect is not alpha7 subunit-dependent and occurs at concentrations likely higher than reached systemically in vivo.

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The effect of noradrenaline (NA) on the efflux of rubidium (⁸⁶Rb) from the rat isolated seminal vesicle was studied in the absence and presence of phentolamine and papaverine. Strips of spirally cut seminal vesicles were incubated in radioactive ⁸⁶Rb (10 μCi·ml^–1) for 2 h. Radioactivity was measured using an autogamma spectrometer, and the flux data were expressed in terms of rate constants per minute, of the reactive isotope efflux. A concentration-effect curve for the effect of NA on rat seminal vesicles was constructed, alone and in the presence of phentolamine (1 μmol/l) or papaverine (5 μmol/l). The results showed that NA (10^–1,000 μmol/l) produced concentration-dependent contractions in the rat seminal vesicle. These responses were greatly reduced by phentolamine but markedly enhanced by papaverine. NA signiñcantly increased ⁸⁶Rb efflux from rat seminal vesicles (control rate constant 0.0042 ± 0.001; test 0.0064 ± 0.002, means ± SE; n = 8 rats; p < 0.001). This increase (52%) occurred within an exposure of 7 ± 1 min to NA. Phentolamine decreased the NA-induced increase in ⁸⁶Rb efflux, by 75 ± 2%, whereas papaverine enhanced it by 86 ± 5 % of the control value. The mechanism of NA-induced increase in ⁸⁶Rb efflux was not further investigated but was interpreted in terms of an increase in intracellular K⁺ (here represented by ⁸⁶Rb), which will leave the cell (efflux) after initial membrane depolarization.

Summary Verapamil (0.05-5 ,1M), diltiazem (0.2-20 /iM), and nifedipine (0.3-30 LM) produced concentration-dependent relaxation of bovine coronary artery. Based on the ECSO values (concentration to produce 50°c maximum response), the calcium entry blocker verapamil (relative potency= l) was 3.4 and 7 times as potent as diltiazem and nifedipine, respectively, in producing relaxation of bovine coronary artery. In addition, verapamil reduced the contractions produced by acetylcholine (0.01-10 RM), 5-hydroxytryptamine (5-HT) (0.01-10 ELM) whereas it potentiated the relaxation produced by noradrenaline (0.01-10 /2M). It was concluded that verapamil, diltiazem, and nifedipine (a) relax the bovine coronary artery, verapamil being more potent than diltiazem and nifedipine, and (b) the calcium entry blockers modified the contractile responses to neurotransmitter agents, acetylcholine, noradrenaline, and 5-HT, inhibiting the contractions produced by acetylcholine and 5-HT, and enhancing the relaxation produced by noradrenaline.