β-Adrenoceptor mediated inhibition by terbutaline of histamine effects on vascular permeability

In guinea‐pigs, previously given Evans blue dye intravenously, 13 to 18 intradermal injections of histamine, with or without other drugs, were made into the depilated trunk skin. Dye was then quantitatively extracted from each skin area and the measured absorbance values were used as a measure of vascular leakage of macromolecules. Histamine (0.5 to 12 nmol) produced dose‐related increases in vascular leakage. These were reduced by terbutaline (1 and 10 nmol) which produced a significant shift in the histamine dose‐response lines to lower absorbance values. The effect of 0.1 nmol of terbutaline was significant only against doses of histamine of less than 2 nmol. Propranolol (1 nmol and 10 nmol) antagonized the effects of terbutaline. Propranolol, at a dose of 10 nmol but not 1 nmol, itself reduced the responses to 1.5 nmol histamine. We conclude that the inhibition by terbutaline of histamine‐induced dye leakage in guinea‐pig skin is mediated by stimulation of β‐adrenoceptors and it is suggested that this effect of terbutaline occurs directly on β‐receptors at the vascular leakage site. 1978 British Pharmacological Societ

An in vitro comparison of β-adrenoceptor stimulants on potassium-depolarized uterine preparations from guinea-pigs

A comparison of six β‐adrenoceptor stimulants has been carried out on in vitro preparations of guinea‐pig uterus which were depolarized in K‐Krebs solution. Results have also been obtained on uterine preparations in which contractions to acetylcholine were inhibited. The establishment of the conditions for the K‐depolarized preparations are described. There was no significant difference between potency values (mean neg log EC values) for any of the drugs on the two types of uterine preparation i.e. the preparations had the same sensitivity to the drugs. There was a less than two‐fold difference between the relative potency values for the β‐adrenoceptor stimulants on the two types of uterine preparation. The relative potency values (isoprenaline = 100) on the K‐depolarized preparation were fenoterol 74.1, salbutamol 15.1, rimiterol 13.5, terbutaline 8.2 and orciprenaline 5.6. The relative potency values obtained on uterine preparations were less than three‐fold different from those previously found for guinea‐pig trachea (after inhibition of extraneuronal uptake). The pA value for propranolol on the K‐depolarized uterine preparations was 9.13. It is concluded that the K‐depolarized guinea‐pig uterine preparation can be used for quantitative studies on β‐adrenoceptor stimulant drugs. It lacks spontaneous activity, drugs can be added cumulatively and several drugs can be compared on a single preparation. In addition, the results obtained support the classification of the β‐adrenoceptors in guinea‐pig uterus and trachea in the same sub‐group (β). 1978 British Pharmacological Societ