PT  - JOURNAL ARTICLE
AU  - S. M. KIRPEKAR
AU  - ROBERT F. FURCHGOTT
TI  - INTERACTION OF TYRAMINE AND GUANETHIDINE IN THE SPLEEN OF THE CAT
DP  - 1972 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 38--46
VI  - 180
IP  - 1
4099  - http://jpet.aspetjournals.org/content/180/1/38.short
4100  - http://jpet.aspetjournals.org/content/180/1/38.full
SO  - J Pharmacol Exp Ther1972 Jan 01; 180
AB  - Interaction between tyramine and guanethidine on postganglionic sympathetic transmission was studied in the cat spleen perfused with Krebs' solution. Both norepinephrine (NE) output and the increase in peripheral resistance caused by sympathetic nerve stimulation at 30/sec were reduced markedly by guanethidine (0.3 µg/ml) within 20 minutes. Further perfusion of the spleen with Krebs' solution alone for over 2 hours caused only a small degree of restoration of NE output. However, after treatment with guanethidine, perfusion of the spleen with tyramine (20 µg/ml) for 20 minutes restored NE output on nerve stimulation to about 50% of the control output, whether or not perfusion with tyramine was continued. Tyramine caused some release of NE in the absence of nerve stimulation, both before and after treatment with guanethidine. Tyramine alone at 20 µg/ml enhanced the output of NE on nerve stimulation, whereas at 200 µg/ml it depressed output. Tyramine (20 µg/ml) enhanced the efflux of 14C-guanethidine from spleens which had been previously exposed to 14C-guanethidine. The reversal by tyramine of the persistent inhibition of NE release after guanethidine treatment, appears to be due to a more rapid loss of guanethidine from the adrenergic nerve terminals. It is proposed that this loss is mainly the consequence of competition between tyramine and guanethidine for intraneuronal binding sites and that it. effectively reduces the concentration of a dissociable complex of guanethidine with an inhibitory receptor. © 1972, by The Williams & Wilkins Company