The Action of Microelectrophoretically Applied (3,4‐dihydroxy‐phenylamino)‐2‐imidazoline (Dpi) on Single Cortical Neurones

Abstract

1The technique of microelectrophoresis was used in order to compare the actions of the imidazoline derivative, (3,4-dihydroxy-phenylamino-2-imidazoline (DPI), with those of dopamine and phenylephrine on single neurones in the cerebral cortex of the rat anaesthetized with halothane. 2 DPI and phenylephrine were almost exclusively excitatory, whereas dopamine could evoke both excitatory and depressant responses. 3 In the case of excitatory responses, DPI appeared to be more potent than dopamine, and was approximately equipotent with phenylephrine. 4 The dopamine antagonist, haloperidol, could discriminate between excitatory responses to DPI and dopamine: responses to dopamine were abolished, whereas responses to DPI, and to a control agonist, acetylcholine, were unaffected. 5 The a-adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to DPI and phenylephrine. Responses to acetylcholine were not affected. 6 It is concluded that DPI does not stimulate dopamine receptors on cortical neurones; the excitatory responses of these cells to DPI may be mediated by ac-adrenoceptors.

The alpha-1 Adrenergic Receptors

“…It is of interest that a similar partial agonistic action of methoxamine has been described at cerebral cortical alpha-1 adrenergic receptors mediating the accumulation of cyclic AMP (Schultz and Kleefeld, 1979) or the hydrolysis of phosphoinositides Kendall et al, 1985), and also at cardiac alpha-1 adrenergic receptors (Schumann and Endoh, 1976). The imidazoline derivative DPI [(3,4-dihydroxyphenyl)-2-iminoimidazoline], which has been reported to be a potent full agonist at alpha-1 adrenergic receptors in vascular smooth muscle , is also a potent excitant of neocortical neurons (Bevan et al, 1979). Although isoproterenol is a relatively selective beta-adrenergic receptor stimulant, at higher dosage levels it can also stimulate alpha-1 adrenergic receptors .…”

“…Phenoxybenzamine, an alpha-1 adrenergic receptor-blocking agent (Minneman, 1983a;Hamilton and Reid, 1985;, is a selective antagonist of excitatory responses to norepinephrine (Bevan et al, 1977(Bevan et al, , 1978(Bevan et al, , 1979Bradshaw et al, 1981Bradshaw et al, , 1983a, phenylephrine (Bevan et al, 1977(Bevan et al, , 1979Bradshaw et al, 1981Bradshaw et al, , 1984a, methoxamine (Bradshaw et al, 1981), DPI (Bevan et al, 1979), and isoproterenol (Bevan et al, 1977). Prazosin, a highly selective and potent alpha-1 adrenergic receptor antagonist (see , selectively and reversibly antagonizes excitatory responses to norepinephrine (Bradshaw et al, 1984a) and phenylephrine (Bradshaw et al, 1982(Bradshaw et al, , 1984a.…”

“…Prazosin, a highly selective and potent alpha-1 adrenergic receptor antagonist (see , selectively and reversibly antagonizes excitatory responses to norepinephrine (Bradshaw et al, 1984a) and phenylephrine (Bradshaw et al, 1982(Bradshaw et al, , 1984a. Haloperidol, a drug that has been reported to be a potent blocker not only of dopamine receptors but also of alpha-1 adrenergic receptors , is effective in selectively antagonizing excitatory neuronal responses to norepinephrine (Bevan et al, 1978;Bradshaw et al, 1983a), phenylephrine (Bradshaw et al, 1983a,b), and DPI (Bevan et al, 1979). On the other hand, excitatory responses to norepinephrine and the alpha-1 adrenergic receptor agonists are relatively resistant to antagonism by the betaadrenergic receptor antagonist sotalol (Bevan et al, 1977) and by the alpha-2 adrenergic receptor antagonists yohimbine and idazoxan (Bradshaw et al, 1982).…”