Influence of the metabolic state on the action of phenylephrine on rabbit ileum, guinea-pig vas deferens and atrium.

Abstract

Under the conditions of altered temperature or metabolic inhibition experiments have been carried out on isolated organs with adrenergic α- and β-receptors, i.e., on rabbit ileum and guinea-pig vas deferens and atrium. Using phenylephrine as a selective α-adrenergic stimulant we were interested to determine whether or not an alteration of the metabolic conditions was capable of causing changes in the affinity of phenylephrine which were identical for the α- and β-receptors. 1. Rabbit Ileum. At 25°C the affinity of phenylephrine to the inhibitory adrenergic α-receptors was 100 times higher than to the β-receptors. Its affinity to the α-receptors was not influenced by raising the temperature or inhibiting the metabolic rate by iodoacetic acid (IAA), whereas that to the β-receptors was diminished to a great extent by raising the temperature. Preincubation at 42°C with the metabolic inhibitor IAA increased the affinity to β-receptors so that it was similar to that at 25°C. 2. Vas Deferens. The excitatory α-mimetic effect of phenylephrine was similarly unaltered by raising the temperature of the bath from 25° to 42°C. IAA did not affect responses to phenylephrine. 3. Guinea-Pig Atrium. An increase of the temperature from 25° to 42°C significantly decreased the affinity of phenylephrine to the β-receptors, whereas IAA at 42°C increased it almost to control values at 25°C. 4. The experiments show that the sensitivity of α-receptors is not altered by an increase of temperature irrespective of whether the α-receptors are mediating inhibitory or excitatory effects, whereas that of the β-receptors is depressed. These results favour the hypothesis that stimulation of α-receptors is independent of, while that of the β-receptors is strongly dependent on the metabolic rate.