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Inhibitory transmitter action of calcitonin gene‐related peptide in guinea‐pig ureter via activation of glibenclamide‐sensitive K channels
Author(s) -
Santicioli Paolo,
Maggi Carlo Alberto
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17030.x
Subject(s) - hyperpolarization (physics) , calcitonin gene related peptide , tetrodotoxin , medicine , endocrinology , chemistry , glibenclamide , inhibitory postsynaptic potential , capsaicin , cromakalim , agonist , neuropeptide , receptor , biology , organic chemistry , nuclear magnetic resonance spectroscopy , diabetes mellitus
1 In single sucrose gap, electrical field stimulation (EFS, 1–5 Hz) produced graded hyperpolarization of the membrane of the guinea‐pig ureter smooth muscle, which was blocked by tetrodotoxin (0.3 μ m ) or in vitro capsaicin desensitization (3 μ m for 15 min). Capsaicin itself produced a transient hyperpolarization of the membrane on its first application. 2 Superfusion with human α calcitonin gene‐related peptide (CGRP, 30–300 μ m ) likewise produced a transient hyperpolarization of the membrane, mimicking the neurogenic inhibitory junction potential (i.j.p.). The hyperpolarization by CGRP was unaffected by tetrodotoxin, indicating a postjunctional site of action. 3 Both the EFS‐evoked i.j.p. and the CGRP‐induced hyperpolarization were inhibited by the CGRP receptor antagonist, CGRP(8–37) (0.3‐3 μ m ) which did not affect the hyperpolarization produced by the K ATP channel opener, cromakalim (0.3 μ m ). 4 The K ATP channel blocker, glibenclamide (1 μ m ) blocked both the EFS‐evoked i.j.p. and the CGRP‐induced hyperpolarization. 5 When evoked in a low K medium (1.2 m m , KC1 being replaced by an equimolar amount of NaC1), the EFS‐evoked i.j.p. and the CGRP‐induced hyperpolarization were both markedly enhanced, consistent with the idea that opening of K channels underlies both responses. 6 The present findings provide direct electrophysiological evidence for a neurotransmitter role of CGRP, released from the peripheral endings of capsaicin‐sensitive primary afferent neurones, in the guinea‐pig ureter. The action of both exogenous and endogenous CGRP involves the activation of glibenclamide‐sensitive (K ATP ) potassium channels.