TY - JOUR
T1 - The actions of receptor-selective substance P analogs on myenteric neurons
T2 - an electrophysiological investigation
AU - Hanani, Menachem
AU - Chorev, Michael
AU - Gilon, Chaim
AU - Selinger, Zvi
PY - 1988/8/24
Y1 - 1988/8/24
N2 - Intracellular recordings were made from myenteric neurons of the guinea-pig duodenum and the responses to local ejection of several substance P (SP) analogs were examined. It was found that senktide (succinyl-[Asp6,Me-Phe8]SP-(6-11), a selective analog for the NK-3 (SP-N) receptor, was particularly effective in depolarizing the neurons. It was 20-100 times more potent than SP and about 1000-fold more potent than the selective analogs for the NK-1 (SP-P) receptor, which resides on muscle cells. The response to the peptides was prolonged (20-120 s), but in about 20% of the cells there was a fast, early depolarizing component (observed only with senktide). In most cases there was an increase in the input resistance of the cell during the slow depolarization. Together with the finding that the response reversed at about -90 mV, this indicates that the response is due to the closure of K+ channels. The results support the existence of an NK-3 (SP-N) receptor and provide direct information about the membrane mechanisms through which NK-3 agonists excite myenteric neurons.
AB - Intracellular recordings were made from myenteric neurons of the guinea-pig duodenum and the responses to local ejection of several substance P (SP) analogs were examined. It was found that senktide (succinyl-[Asp6,Me-Phe8]SP-(6-11), a selective analog for the NK-3 (SP-N) receptor, was particularly effective in depolarizing the neurons. It was 20-100 times more potent than SP and about 1000-fold more potent than the selective analogs for the NK-1 (SP-P) receptor, which resides on muscle cells. The response to the peptides was prolonged (20-120 s), but in about 20% of the cells there was a fast, early depolarizing component (observed only with senktide). In most cases there was an increase in the input resistance of the cell during the slow depolarization. Together with the finding that the response reversed at about -90 mV, this indicates that the response is due to the closure of K+ channels. The results support the existence of an NK-3 (SP-N) receptor and provide direct information about the membrane mechanisms through which NK-3 agonists excite myenteric neurons.
KW - Myenteric plexus
KW - Senktide
KW - Substance P
KW - Substance P analogs
KW - Tachykinins
UR - http://www.scopus.com/inward/record.url?scp=0023726748&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(88)90612-7
DO - 10.1016/0014-2999(88)90612-7
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C2 - 2460360
AN - SCOPUS:0023726748
SN - 0014-2999
VL - 153
SP - 247
EP - 253
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -