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).