Pharmacological characterization of the receptor mediating the adrenergic inhibition of responses to substance P in the cingulate cortex.
The excitatory responses of neurones in the anterior cingulate cortex of the rat to iontophoretically applied substance P (SP) are reduced by noradrenaline (NA) applied iontophoretically or released from noradrenergic pathways. In order to determine the receptor involved in this inhibitory effect we have studied the effects of a number of receptor-specific adrenergic agonists and antagonists on responses of cingulate neurones to SP in rats anaesthetized with chloral hydrate. Low iontophoretic currents (0-15 nA) of NA, adrenaline and the beta-agonist, clenbuterol, all strongly reduced responses to SP. Isoprenaline was also effective but less consistently so, although problems were experienced with its iontophoretic release from micropipettes. The alpha 1-agonists, phenylephrine and methoxamine were also able to reduce responses to SP. However, this reduction required higher iontophoretic currents (15-60 nA) and was associated with depressant effects on baseline firing rate. The alpha 2-agonist clonidine was only weakly active at high currents and this too was associated with depression of baseline firing. Similar weak effects were noted with dopamine. The inhibitory effects of NA on SP responses were convincingly blocked or reversed by the beta-antagonist, practolol, but not by the alpha 1-antagonist, prazosin. The reduction of SP responses by phenylephrine was also blocked by practolol but unaffected by prazosin. Finally, reduction of SP excitations by activation of the coeruleocortical pathway was also blocked by practolol applied iontophoretically to the cortical cells. These results are consistent with the hypothesis that the effect of NA on SP responsiveness in the cingulate cortex is mediated by beta-adrenoreceptors.
R S
RS
Jones
H R
HR
Olpe
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011217:Practolol / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors*
D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D013373:Substance P; D003000:Clonidine; D000420:Albuterol; D011217:Practolol; D004298:Dopamine; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine