Temperature‐induced interconversion of alpha‐and beta‐adrenoceptors in the frog heart.

Abstract

SUMMARY1. The effect of ambient temperature on the properties of adrenoceptors mediating inotropic responses was assessed in isolated frog hearts on the basis of the effects and tissue uptake of ox-and fl-adrenoceptor antagonists.2. At temperatures of 230 C and above inotropic responses to adrenaline were antagonized by propranolol (0-4-4.0 uM), but were unaffected by phentolamine (26.5 AM) and were potentiated by phenoxybenzamine (POB) (0.7-29.5 AM). Below 170 C the activity of propranolol was reduced at least tenfold, and the a-adrenoceptor antagonists inhibited responses to both adrenaline and isoprenaline, but not those to CaC12.3. The responses of hearts exposed to POB at 140 C and then tested, after thorough washing, at both 14 and 240 C were similarly inhibited at both temperatures, i.e. the usual fl-adrenoceptor response did not appear at the higher temperature. Conversely, exposure to POB at 240 C produced only potentiation at both test temperatures.4

Cardiac Adrenoceptors at Low Temperature and the Adrenoceptor Interconversion Hypothesis

“…It has further been reported that at low temperature the fl-adrenoceptorblocking drug propranolol loses 90% of its potency as an antagonist of the inotropic effect of adrenaline on the frog heart (Kunos & Nickerson, 1976). The problem is that the time of treatment with propranolol was very short, which raises the question whether the receptor blockade was complete.…”

“…For example, temperature reduction from 250C to 12°C caused a tenfold increase in the chronotropic potency of adrenaline in the perfused toad heart (Harri, 1973) but temperature reduction from 240C to 140C led to a tenfold crease in the inotropic potency of adrenaline in the frog isolated heart (Kunos & Nickerson, 1976). At 120C isoprenaline was more potent than phenylephrine in the perfused toad heart (Harri, 1973) and frog heart (Tirri, Harri & Laitinen, 1974); at 14°C isoprenaline was more potent than phenylephrine in the frog ventricle (Benfey, 1975).…”

“…It has been suggested that a-and faadrenoceptors are 'conformations' of a single adrenoceptor (Kunos & Szentivanyi, 1968;Kunos, Yong & Nickerson, 1973;Kunos & Nickerson, 1976). The following observation in the isolated heart of the frog has been accepted as proof of receptor interconversion (Kunos et al, 1973;Kunos & Nickerson, 1976). The a-adrenoceptor blocking drug phenoxybenzamine inhibits the inotropic effect of adrenaline at low temperature and not at higher temperature; however, the adrenaline effect is inhibited at high temperature if the heart is pretreated with phenoxybenzamine at low temperature.…”

“…It has also been reported that adenylate cyclase-coupled f,-adrenoceptors in frog, rat and dog heart do not change with temperature (Benfey et al, 1974;Caron &Lefkowitz, 1974). Kunos et al (1973), Benfey et al (1974) and Kunos & Nickerson (1976) did not work under 'optimal conditions in experiments for the pharmacological characterization of adrenoceptors in isolated tissues' (Furchgott, 1972 Before exposure to drugs the heart preparations were maintained at a given temperature for at least an hour. Incubation with propranolol or phentolamine was for 1 h or more.…”

Alpha-adrenergic receptors in rat myocardium. Identification by binding of [3H]dihydroergocryptine.

“…38 ' 42 The capacity to assess directly both species of receptors after interventions known to influence the relative magnitudes of the respective physiological responses to a-and ^-stimulation should be of use in resolving this provocative issue.…”