Antagonism by β‐adrenoceptor blocking agents of the antianaphylactic effect of isoprenaline

Summary1. Isoprenaline (002 to 2-0 ,ug kg-' min-') inhibited gastric secretion in response to pentagastrin in both conscious and anaesthetized dogs and in response to feeding in conscious dogs.2. The inhibition was unaffected during cardiac f8-adrenoceptor blockade by propranolol. 3. The inhibition was not due to decreased mucosal blood flow. 4. This effect of isoprenaline is different from its effect on histamine-induced gastric secretion. 5. Noradrenaline (005-2-0 ,ug kg-' min') also decreased gastric secretion but it was less effective than isoprenaline. 6. The mechanism of action of noradrenaline is probably a decrease in mucosal blood flow. IntroductionThe effect of an adrenoceptor stimulant drug on gastric secretion depends on many factors, particularly whether it acts on a-or ,8-receptors and whether secretion is induced by histamine or by gastrin-like compounds. This field has recently been reviewed by Holton (1972). The mechanism of action of noradrenaline, an .a-adrenoceptor agonist, appears to be primarily by the production of a decrease in mucosal blood flow (Jacobson, 1970). The mechanism of action of the 3-adrenoceptor agonist, isoprenaline, is more complex. On a background of histamine stimulation, small doses of isoprenaline increase or do not affect secretion

Section: Discussionmentioning

confidence: 99%

The effects of isoprenaline and noradrenaline on pentagastrin‐stimulated gastric acid secretion and mucosal blood flow in the dog

Curwain

Holton

1972

“…These drugs inhibited histamine release incompletely (Assem & Schild,197 lb), which suggests that they possess a partial agonist effect on leucocyte (basophil) p-receptors. While propranolol and practolol both acted as antagonists to isoprenaline in histamine release studies (Assem & Schild, 1971b), only propranolol antagonized the effect of isoprenaline on HFC, practolol having little or no effect. Propranolol therefore not only blocked the action of isoprenaline but, like a physiological antagonist, itself produced the opposite effect to that of isoprenaline.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sympathomimetic Amines on the Histamine Forming Capacity of Human Leucocytes

Assem

1974

1The effects of at-and ,B-adrenoceptor stimulants on the histamine-forming capacity (HFC) of human isolated leucocytes have been studied, in vitro. 2 It was confirmed that antigen significantly stimulates the HFC of human leucocytes.3 ,B-Adrenoceptor stimulants, such as isoprenaline and salbutamol (10 -610 3 M) significantly inhibited the HFC of human leucocytes in the presence and absence of antigen. At concentrations lower than 10-6 M, this effect was not observed. In general the degree of inhibition of HFC by 3-adrenoceptor stimulants followed their potency as 3-adrenoceptor stimulants. 4 a-Adrenoceptor stimulants significantly stimulated leucocyte HFC; noradrenaline within a limited concentration of 1 -6 M, while stimulation was seen consistently with phenylephrine at concentrations of 10--10 M. Adrenaline, which stimulates both aX-and ,B-adrenoceptors, produced small inhibition, no effect, or a degree of stimulation. Phentolamine, an ca-adrenoceptor blocking agent, produced an effect opposite to that of the a-adrenoceptor stimulants, i.e. a significant inhibition of the HFC of human isolated leucocytes.

“…The subclassification of f-adrenoceptors into two distinct types termed fl-and 12-adrenoceptors (Lands, Arnold, McAuliff, Luduena & Brown 1967) is now generally accepted. However, there is evidence that the f-adrenoceptor present, presumably on the mast cell, which mediates the antianaphylactic activity of f-adrenoceptor agonists in guinea-pig lung may differ from both ,B,-and 12-subtypes (Assem & Schild, 1971;Sorenby, 1975;Malta & Raper, 1975 (± -erythro-2-isopropylamino-l-(4-tolyl)-1 -propanol: AB Hassle); FPL 55712 (8-propyl-7-{3-(4-acetyl-2-propyl-3-hydroxyphenoxy)-2-hydroxyproxy} -4-oxo-4H-benzopyran-2-carboxylic acid) synthesized by Dr D. Brickwood, Glaxo Group Research Limited; atropine sulphate (BDH).…”

Section: Introductionmentioning

confidence: 99%

“…Methods fB-Adrenoceptor agonists inhibit the anaphylactic release of histamine and slow reacting substance of anaphylaxis (SRS-A) from human lung tissue (Orange, Kaliner, LaRaia & Austen, 1971;Strandberg, Pegelow, Persson & S6renby, 1979;Butchers, Fullarton, Skidmore, Thompson, Vardey & Wheeldon, 1979) and from guinea-pig lung (Assem & Schild, 1971;Malta & Raper, 1975;Sorenby, 1975;Forsberg & Sorenby, 1979). The subclassification of f-adrenoceptors into two distinct types termed fl-and 12-adrenoceptors (Lands, Arnold, McAuliff, Luduena & Brown 1967) is now generally accepted.…”

Section: Introductionmentioning

confidence: 99%

CHARACTERIZATION OF THE RECEPTOR MEDIATING THE ANTI‐ANAPHYLACTIC EFFECTS OF β‐ADRENOCEPTOR AGONISTS IN HUMAN LUNG TISSUE in vitro

Butchers

Skidmore

Vardey

et al. 1980