Pharmacological investigation of alpha-adrenoreceptors in guinea-pig splenic capsule.

1. A study has been made of alpha-adrenoreceptors in the smooth muscle of the guinea-pig splenic capsule. 2. In this preparation, noradrenaline (NA), adrenaline (Adr) and alpha-methyl-NA were full agonists, while phenylephrine, dopamine and the catechol-imidazolidine (3,4-dihydroxyphenylamino)-2-imidazolidine, (DPI) were partial agonists. 3. The imidazolidines clonidine and oxymetazoline showed no agonist activity, but both inhibited the agonist activity of NA. pA2 values calculated from Arunlakshana and Schild plots were 6.88 and 6.95 for clonidine and oxymetazoline respectively. Slopes of the Schild plots were close to unity, indicating competitive antagonism. 4. The alpha-adrenoreceptor antagonists phentolamine, prazosin and yohimbine also inhibited the agonist activity of NA with man pA2 values of 8.32, 9.22 and 6.90 respectively. Slopes of Schild plots were significantly less than 1, suggesting that the inhibition was not truly competitive in nature. 5. The irreversible alpha-adrenoreceptor antagonist phenoxybenzamine at low concentrations (10(-9)M) shifted the log concentration-response curve to NA to the right and greatly reduced the maximum response. 6. It is suggested that the adrenoreceptors in the guinea-pig splenic capsule are probably of the alpha 1-type, and that this tissue possesses relatively few spare receptors.