Strong activation of vascular prejunctional beta 2-adrenoceptors in freely moving rats by adrenaline released as a co-transmitter.
The effect of adrenaline on the electrically evoked noradrenaline overflow in the portal vein of adrenal demedullated freely moving rats was studied. Adrenaline (100 ng/min) was infused for 2 h into the portal vein. After a 1-h interval when plasma adrenaline had returned to pre-infusion undetectable levels, the portal vein nervus plexus was electrically stimulated. During stimulation (2 Hz, 3 ms, 5 mA) adrenaline and noradrenaline were released. The stimulus-evoked noradrenaline overflow was facilitated to 194% of the control-evoked overflow (infusion of saline). Total catecholamine overflow (noradrenaline plus adrenaline) was enhanced to 258%. The facilitation of the evoked overflow of both noradrenaline and adrenaline was blocked by the selective beta 2-adrenoceptor antagonist, ICI 118,551 (0.3 mg/kg). Cocaine (2.5 mg/kg plus 0.05 mg/kg per min) infused together with adrenaline prevented the evoked release of adrenaline and no facilitation of the stimulus-induced noradrenaline overflow occurred. Inhibition of prejunctional inhibitory alpha 2-adrenoceptors with yohimbine (0.5 mg/kg) further enhanced, to 577%, the electrically evoked catecholamine overflow after adrenaline infusion. The results demonstrate that adrenaline can be taken up by sympathetic nerve endings through cocaine-sensitive uptake carriers, and is released from these nerves during electrical stimulation of the portal vein nervus plexus. Neuronally released adrenaline can strongly facilitate electrically evoked neurotransmitter overflow through activation of prejunctional beta 2-adrenoceptors.
Coppes
R P
RP
Department of Pharmacology and Therapeutics, University of Groningen, Netherlands.
Smit
J
J
Khali
N N
NN
Brouwer
F
F
Zaagsma
J
J
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D004837:Epinephrine / Q000378:metabolism* / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology; D008297:Male; D011169:Portal Vein / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D003042:Cocaine; D004837:Epinephrine