Casey P. Robinson

Vascular effects of demethylchlordimeform, a metabolite of chlordimeform

Abstract Demethylchlordimeform causes contractions of the rabbit central ear artery in concentrations from 10 −9 – 10 −4 M . The maximal contraction is approximately 40% of the maximal contraction to norepinephrine and is obtained with 10 −4 M . Neither 0.1 mg/ml of atropine, pyribenzamine, nor methysergide affected these contractions, but 0.001 mg/ml of phentolamine reduced, and 0.1 mg/ml of phentolamine almost abolished them. These contractions are not decreased in reserpinized rabbits. Demethylchlordimeform does not alter norepinephrine efflux in the resting state, during electrical stimulation, or during nicotine stimulation. In addition to its agonist activity it also antagonizes contractions of the vascular strip caused by two vasoactive agents. A concentration of 10 −5 M antagonizes contractions caused by norepinephrine and potassium but not by serotonin and histamine. Thus, demethylchlordimeform contracts vascular tissue as a partial agonist at α-adrenergic receptors and also antagonizes contractions induced by vasoactive agents.

Lack of involvement of monoamine oxidase inhibition in the lethality of acute poisoning by chlordimeform

Depletion of serotonin or norepinephrine in male rats by pretreatment with p-chlorophenylalanine or DL-alpha-methyl-p-tyrosine, respectively, failed to reduce the lethality of the monoamine oxidase-inhibiting acaricide, chlordimeform. Administration of phenylephrine, a directly acting alpha-adrenergic agonist, with chlordimeform did not increase the lethality of chlordimeform. Thus, monoamine oxidase inhibition by chlordimeform does not seem to contribute to its lethality.

Effects of Palytoxin on Guinea Pig Tracheal Strips

The effects of palytoxin (PTX) on airway smooth muscle were investigated in opened rings of guinea pig trachea. Concentrations of PTX from 10 pM to 100 nM caused contractions of tracheal strips, with maximal contractions approximately 80% of those in response to 120 mM potassium. Tension increased to its maximum in approximately 5 min with 100 nM PTX, then decreased to or near resting tension over the next 60 min. Contractions were larger when the epithelium was removed. Exposure to high (100 nM) concentrations of PTX markedly reduced subsequent contractions to PTX but had less effect on potassium-induced contractions. In zero-calcium solution the rate of contraction was slowed but the maximal contraction was not reduced. The addition of a calcium channel blocker (verapamil) markedly reduced the contractions and a calcium chelator (EGTA) abolished them. Contractions to PTX in zero-calcium media suggested that tracheal cartilage was serving as a calcium source, as it has been previously reported to do. Potassium removal and sodium reduction also greatly reduced contractions. These data are consistent with other observations suggesting that PTX may form pores through which sodium leaks into the cell. PTX was also found to differ from ouabain in its mode of action.

Lack of an effect of saxitonin on the contractility of isolated guinea-pig trachea, lung parenchyma and aorta

The effects of saxitonin were investigated in guinea-pig tracheal rings, lung parenchymal strips and aorta rings. Tracheal rings were used both with epithelium present and with it removed. Aorta rings were used both with endothelium present and with it removed. Saxitoxin, 1 pM to 0.1 microM, did not alter the resting tension of either airway tissues or aorta. Also 0.1 microM saxitonin did not reduce tension of tracheal rings contracted by 10 microM carbachol, parenchymal strips contracted by 100 microM acetylcholine or by 10 microM histamine, or aorta rings contracted by 10 microM norepinephrine. Responses of tracheal rings to 0.03-10 microM carbachol added cumulatively were not altered by 0.1 microM saxitoxin (EC50 with epithelium: 1.11 +/- 0.48 microM control, 2.01 +/- 0.71 microM with saxitoxin; EC50 without epithelium: 2.83 +/- 0.55 microM control, 2.05 +/- 0.58 microM with saxitoxin). Also, 1 microM saxitoxin did not alter contractions of parenchymal stirps to cumulatively added acetylcholine (EC50: 3.47 +/- 1.06 microM, control; 3.98 +/- 1.19 microM with saxitoxin), histamine (EC50: 0.83 +/- 0.24 microM, control; 0.60 +/- 0.13 microM with saxitoxin); or of aorta strips to norepinephrine with endothelium (EC50: 1.78 +/- 0.80 microM, control; 0.74 +/- 0.21 microM with saxitoxin) or without endothelium (EC50: 2.18 +/- 0.78 microM, control; 1.42 +/- 0.62 microM with saxitoxin). Thus, saxitoxin did not significantly alter contractile activity of airways of large arteries in vitro.

Effects of soman on norepinephrine uptake and electrically stimulated release from human uterine arteries

The effects of soman on the uptake and electrically induced release of norepinephrine (noradrenaline) from isolated human uterine artery have been investigated. Soman did not alter the uptake of norepinephrine by human uterine artery, but reduced the electrically induced release of norepinephrine from the artery. This reduced norepinephrine release may augment the fall in blood pressure induced by accumulated acetylcholine stimulating muscarinic receptors following cholinesterase inhibition.