Cardiac Adrenoreceptors

1Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments from the atrial and right ventricular free walls of rat hearts during superfusion and electrical stimulation in vitro at 37°C. 2 Availability of the fast sodium channels for current flow was inferred from the maximum rate of rise of membrane potential during phase 0 of the action potential. 3 Phentolamine mesylate (2 to 20 LM) caused a concentration-dependent block of the fast sodium channel. This was reflected in prolongation of the refractory period and slowing of recovery of excitability following the action potential, without significant change in action potential duration or resting membrane potential. 4 Increase in the concentration of KCI in the superfusate from 5 to 10 mm depolarized the muscle and potentiated the blocking action of phentolamine. Both the depolarizing and the phentolaminepotentiating actions of KCI were counteracted by simultaneous elevation of the concentration of CaC12 in the superfusate from 2 to 10 mM. 5 The blocking action of phentolamine was enhanced by increasing the frequency of electrical stimulation in the range 0.01 to 10 Hz. 6 In respect of the properties listed above, lignocaine hydrochloride was similar to phentolamine but was different from quinidine sulphate in that the effects of the latter drug were not potentiated by KCl. 7 Two other ac-adrenoceptor antagonists, prazosin and yohimbine, both displayed actions similar to those shown by phentolamine. Tolazoline was only weakly active and dihydroergotamine (60 pM) was inactive. Dibenamine and phenoxybenzamine, unlike the previously named drugs, caused an irreversible block of the fast sodium channel. These blocking actions of oa-adrenoceptor antagonists were not prevented by simultaneous exposure to the ot-adrenoceptor agonist phenylephrine (1 mm). 8 Muscle from both reserpine pretreated and non-pretreated rats responded indistinguishably to phentolamine.

Section: Discussionmentioning

confidence: 51%

A comparison of the electrophysiological actions of phentolamine with those of some other antiarrhythmic drugs on tissues isolated from the rat heart

Northover

1983

“…In rat vas deferens preparations, xamoterol s mean concentration-(10-75i1moll1') produced parallel shifts in (-)-ne in the absence and isoprenaline curves, and the slope function 1984), P2-adrenoceptors (oestrogen-pretreated guineapig uterus, rat vas deferens, oestrogen-pretreated rat uterus; Krstew et al, 1982;Kenakin, 1982) (Broadley, 1982) Cook et al (1984) who published results of radioligand binding studies with xamoterol using rat and rabbit lung membrane homogenates.…”

Section: Resultsmentioning

confidence: 99%

The in vitro pharmacology of xamoterol (ICI 118,587)

Malta¹,

Mian²,

Raper³

1985

IThe effect of xamoterol and (-)-isoprenaline have been compared for their activity at padrenoceptor sites in a number of in vitro cardiac and smooth muscle preparations. 2 Xamoterol produced weak positive chronotropic effects in guinea-pig, rat and cat atria (intrinsic activity < 0.55, ( -)-isoprenaline = 1). Positive inotropic effects were obtained in driven left atria of the cat but were absent in guinea-pig left atrial and right ventricular strip preparations. Agonistic effects were due to P,-adrenoceptor stimulation. 3 Xamoterol was without P-adrenoceptor-mediated inhibitory effects in guinea-pig ileal, tracheal and uterine preparations and in the rat vas deferens and oestrogen-primed uterus. Weak P2-adrenoceptor-mediated relaxation was obtained in progesterone-primed rat uteri. 4 Xamoterol produced non-specific inhibitory effects in guinea-pig ileal and tracheal preparations.5 Xamoterol acted as a competitive antagonist at P,-(pA2 range = 7.4 to 7.8) and P2-adrenoceptors (pA2 range 5.2 to 6.2) and displaced ['251]-iodocyanopindolol from guinea-pig left atrial (pKD = 7.25) and uterine (pKD 5.24) membrane preparations. 6 It is concluded that xamoterol displays a selective affinity for p,-adrenoceptors. Although its partial agonistic actions are more evident at P,-adrenoceptor sites, like prenalterol, xamoterol displays a degree of tissue rather than receptor-dependent selectivity.

“…The tissues used were the left atria and uterus from the guinea-pig, since mechanical responses in these tissues have been shown to be initiated via homogeneous populations of 13i-and 12-adrenoceptors respectively (Broadley, 1982;Krstew et al, 1982). Of crucial importance in such a study is the accurate assessment of the dissociation constant (1/affinity constant) of the agonist, since the computation of efficacy utilizes this value.…”

Section: Introductionmentioning

confidence: 99%

The affinity and efficacy of the selective β₁‐adrenoceptor stimulant RO363 at β₁‐ and β₂‐adrenoceptor sites

McPherson¹,

Malta²,

Molenaar³

et al. 1984

1(-)-Isoprenaline and the selective P1-adrenoceptor agonist R0363 were tested for their inotropic effects in left atrial (1i,) 3 The pKD values for (-)-isoprenaline were similar in the two tissues (left atria 6.4, uterus 6.0) whilst for R0363 the atrial value (7.8) was considerably greater than that for the uterus (6.0). The latter value is very similar to the pKB value determined from shifts in (-)-isoprenaline curves produced by R0363 in uterine preparations. 4 Graphical plots of the fraction of receptors occupied vs response were constructed. The relative efficacy of (-)-isoprenaline with respect to R0363 was calculated to be 25 in atrial and 2633 in uterine preparations.5 The selective Pf-adrenoceptor stimulant actions of R0363 are a reflection of both its greater affinity and efficacy for Pl-as opposed to P2-adrenoceptor sites. The potent actions of (-)-isoprenaline in both tissues are largely dependent on efficacy.