Resistance of adrenergic neurotransmission in the toad heart to adrenoceptor blockade

Abstract

Stimulation of sympathetic nerves to the toad heart produced increases in both the rate and force of cardiac beat. Although these responses were abolished by treatment with bretylium (10-6 mol.1-1) or 6-hydroxydopamine (100 mg.kg-1), and surgical sympathetic denervation, they were not abolished by treatment with propranolol (10-6 mol-1-1) and phentolamine (3 X 10-6 mol.1-1), either alone or in combination. The responses remaining after adrenoceptor blockade could not be ascribed to the effects of neurally released dopamine, ATP, adenosine, histamine or a variety of neuropeptides, although the participation of an as yet unidentified co-transmitter cannot be ruled out. Quantitative analysis of the interactions between propranolol and adrenaline on cardiac adrenoceptors, after blockade of alpha-receptors and amine uptake mechanisms, revealed that these interactions do not comply with the conditions for simple competitivity. Therefore, in addition to its action on beta-receptors, adrenaline seems to be producing excitation of the toad heart by acting on adrenoceptors which cannot be classified as either alpha- or beta-receptors. These results, together with the existence of close neuromuscular gaps (less than 50 nm) in the toad heart, are consistent with the hypothesis that sympathetic excitation of the toad heart is mediated by both "extra-junctional" beta-adrenoceptors, and "junctional" adrenoceptors which are neither alpha- nor beta-receptors.

Effects of sympathetic nerve stimulation on the sino‐atrial node of the guinea‐pig.

“…In amphibian hearts, the responses to sympathetic nerve stimulation are largely resistant to ,-adrenoceptor blockade (Morris et al 1981). Rather, neurally released adrenaline activates a dihydroergotamine-sensitive catecholamine receptor and only escapes to cardiac ,3-adrenoceptors if amine uptake systems are blocked (Bramich et al 1990.…”

“…For example, amphibian pacemaker cells possess f8-adrenoceptors (O'Donnell & Wanstall, 1982) linked to a cyclic AMP-dependent pathway (Hartzell, 1988;Bramich, Brock, Edwards & Hirst, 1993). However, sympathetic tachycardias recorded from these preparations are little affected by fadrenoceptor antagonists (Morris, Gibbins & Clevers, 1981;Bramich, Edwards & Hirst, 1990). These observations initially led to the suggestion that either neuronally released adrenaline activates a specialized junctional adrenoceptor (Morris et al 1981) or that the primary sympathetic transmitter is a purine, perhaps adenosine 5'-triphosphate (ATP), rather than adrenaline (Hoyle & Burnstock, 1986).…”

“…However, sympathetic tachycardias recorded from these preparations are little affected by fadrenoceptor antagonists (Morris, Gibbins & Clevers, 1981;Bramich, Edwards & Hirst, 1990). These observations initially led to the suggestion that either neuronally released adrenaline activates a specialized junctional adrenoceptor (Morris et al 1981) or that the primary sympathetic transmitter is a purine, perhaps adenosine 5'-triphosphate (ATP), rather than adrenaline (Hoyle & Burnstock, 1986). More recently the suggestion has been made that sympathetic transmission at these cells might involve the co-activation of specialized junctional adrenoceptors and specialized purinoceptors (Bramich et al 1990).…”

Responses to sympathetic nerve stimulation of the sinus venosus of the toad.

“…7A and B). The rate of beating rapidly increased during the stimulation train then in most preparations fell back towards control levels (Morris et al 1981;Bramich et al 1990). Subsequently the rate of beating increased to remain above control levels for some 10-20 min.…”

“…However, as pointed out, much of the chronotropic, and part of the inotropic. response to sympathetic nerve stimulation does not depend upon the activation of ,-adrenoceptors (Morris et al 1981;Bramich et al 1990). These experiments aimed to compare the responses produced when a cyclic AMP pathway was activated with the responses produced by sympathetic nerve stimulation.…”