Capsaicin and sensory neuropeptide stimulation of goblet cell secretion in guinea-pig trachea.
1. We studied the effect of capsaicin and sensory neuropeptides on tracheal goblet cell secretion in anaesthetized guinea-pigs using a semi-quantitative morphometric technique whereby the magnitude of discharge of stained intracellular mucus, expressed as a mucus score (MS), was related inversely to discharge. 2. Capsaicin (i.v.) induced goblet cell secretion: a decrease of 50% in MS below control (indicative of increased secretion) was maximal at 3.3 x 10(-9) mol/kg. 3. Capsaicin-induced secretion was unaffected either by prior vagus nerve section or by pre-treatment with atropine, propranolol and phentolamine which suggests that local axon reflexes with release of sensory neuropeptides are involved in the response. 4. Intravenous substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide (CGRP) produced dose-related increases in goblet cell secretion, with SP the most potent. Doses (mol/kg) causing a 50% decrease in MS from control were 3.5 x 10(-12) for SP; 72 x 10(-10) for NKA; 1.6 x 10(-9) for NKB; and 1.2 x 10(-8) for CGRP. The maximal increase in goblet cell secretion was 75% of control and occurred with SP at 10(-10) mol/kg. 5. SP-induced mucus discharge was not inhibited by atropine or the histamine receptor antagonists mepyramine or cimetidine. 6. We conclude that in guinea-pig trachea, goblet cell secretion is under the control of capsaicin-sensitive sensory nerves and release of neuropeptides from these nerves may induce mucus discharge via tachykinin receptors of the NK-1 subtype (indicated by an order of potency of SP greater than NKA greater than NKB).
Kuo
H P
HP
Department of Thoracic Medicine, National Heart & Lung Institute, London.
Rohde
J A
JA
Tokuyama
K
K
Barnes
P J
PJ
Rogers
D F
DF
D000768:Anesthesia, General; D000818:Animals; D001369:Axons / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005088:Exocrine Glands / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D009093:Mucus / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors; D014132:Trachea / Q000187:drug effects*
D009479:Neuropeptides; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin