AN in vitro COMPARISON OF β‐ADRENOCEPTOR STIMULANTS ON POTASSIUM‐DEPOLARIZED UTERINE PREPARATIONS FROM GUINEA‐PIGS

Abstract

1A comparison of six P-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. 2 There was no significant difference between potency values (mean neg log EC50 values) for any of the drugs on the two types of uterine preparation i.e. the preparations had the same sensitivity to the drugs. 3 There was a less than two-fold difference between the relative potency values for the ,B-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. 4 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). 5 The pA2 value for propranolol on the K+-depolarized uterine preparations was 9.13. 6 It is concluded that the K+-depolarized guinea-pig uterine preparation can be used for quantitative studies on P-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 ,B-adrenoceptors in guinea-pig uterus and trachea in the same sub-group (#2).

Expression of Messenger RNA Coding for 5‐HT Receptor, Alpha and Beta Adrenoreceptor (Subtypes) during Oestrus and Dioestrus in the Bovine Uterus

“…Adrenergic receptors belong to the cell surface G‐protein‐coupled receptors. In the bovine, adrenergic stimulation causes both contraction and relaxation of the uterine smooth muscles through α‐excitatory and β 2 ‐inhibitory adrenoreceptors respectively (O'Donnell et al., 1978; Digges, 1982). Functional studies indicate that α 2 ‐AR is the most abundant; however, both α 1 and α 2 ‐AR mediate contractions of the smooth muscles of the bovine uterus (Taneike et al., 1999).…”

β2‐Adrenoceptor blockade is the basis of guinea‐pig bronchial hyper‐responsiveness to leukotriene C4 and other agonists

“…Experiments on the vascular system of our preparation turned out to be hardly practicable, because of the weak and erratic hypotension obtained with P2-agonists. On the other hand, significant evidence has been obtained in experiments performed on the guinea-pig uterus in situ, an organ rich in 12-adrenoceptors (O'Donnell, Persson & Wanstall, 1978). In fact, doses of "-blockers able to trigger bronchial hyper-responsiveness were also able to antagonize the utero-relaxant effects of fenoterol (10 nmol kg-, i.v.)…”

Effects of Non-Selective and Selective Beta-Adrenergic Agonists on Spontaneous Contractions and Cyclic AMP Levels in Myometrial Strips from Pregnant Women

“…During the last years this effect has led to an extensive use of /3-adrenomimetic drugs in clinical practice, especially to prevent premature labout (2 ,4 -8). Since the /3-receptors in the uterus predominately belong to the /32-subtype (3,20,21), /32-selective agonists, such as terbutaline and salbutamol, are preferred in order to diminish side effects due to Pi -receptor stimulation.…”