Modulation of neurotransmission in the guinea‐pig vas deferens by capsaicin: involvement of calcitonin gene‐related peptide and substance P

Abstract

1 The effects of capsaicin, calcitonin gene-related peptide and substance P were studied via three parameters in the guinea-pig vas deferens: the overflow of ATP and of tritiated noradrenaline, the mechanical responses to field stimulation and the mechanical responses to exogenous noradrenaline and a4,-methylene ATP. 2 At 2 Hz, capsaicin inhibited the stimulus-evoked release of ATP, whereas it was without effect on the release of noradrenaline. At 20 Hz capsaicin did not affect the release of either of the cotransmitters. Capsaicin enhanced responses to a,fi-methylene ATP, but not to exogenous noradrenaline. 3 Calcitonin gene-related peptide, like capsaicin, inhibited the release of ATP, but not noradrenaline at 2 Hz and was without effect on release at 20 Hz. However, calcitonin gene-related peptide inhibited responses to a,,B-methylene ATP and was without effect on responses to exogenous noradrenaline. 4 Substance P had no effect on the release of either noradrenaline or ATP at either frequency. However, like capsaicin it enhanced responses to a,,B-methylene ATP and was without effect on exogenous noradrenaline. 5 These results suggest that the actions of capsaicin on the guinea-pig isolated vas deferens are mediated via the release of both calcitonin gene-related peptide and substance P. Furthermore, as capsaicin and calcitonin gene-related peptide prejunctionally modulate purinergic, but not noradrenergic transmission, this suggests that the mechanisms for the storage and release of the sympathetic co-transmitters noradrenaline and ATP may not be the same.

Novel selective agonists and antagonists confirm neurokinin NK1 receptors in guinea‐pig vas deferens

“…The site of action of tachykinins in the guinea-pig vas deferens is unclear. A postjunctional site on the smooth muscle has been suggested by Ellis & Burnstock (1989) longitudinal muscle of the guinea-pig vas deferens, and post-junctional neurokinin (NK1) receptors on the innner longitudinal smooth muscle has been proposed from autoradiographic studies (Mussop et al, 1989). It therefore seems unresolved whether both pre-(on sensory or sympathetic) and post-junctional receptors are functionally involved in the potentiation of twitch responses by tachykinins.…”

“…However, since its original classification as an SP-P (= NK1) (Watson et al, 1983), this preparation has been little studied in terms of neurokinin receptor subtypes or involvement of other mediators in responses to tachykinins. Pharmacological investigation of the site of action of tachykinins (Ellis & Burnstock, 1989) and the autoradiographic localisation of neurokinin receptors (Mussop et al, 1989) have, however, recently been reported. The rat vas deferens in contrast has been used extensively to study sympathetic neuromodulation, though here tachykinin action is mediated through interaction with NK2 receptors.…”

ATP overflow from the mouse isolated vas deferens

“…When 100 pulses were applied, stimulated-ATP increased by 14.23 and 28 times above spontaneous levels (groups C and D). In the guinea-pig vas deferens, Ellis & Burnstock (1989) reported levels of ATP following stimulation of 1.95 ± 1.17 (n = 6) times above spontaneous levels at 2 Hz and 6.30 ± 1.11 (n = 6) times at 20 Hz, even so, the number of pulses used (240 pulses) was much higher. Kirkpatrick & Burnstock (1987) reported at 16 Hz a 50 fold increase of ATP efflux above spontaneous levels of release.…”

Inhibitory effects of capsaicin on acetylcholine‐evoked responses in rat phaeochromocytoma cells

“…The concentration of capsaicin that maximally activates non-specific cation channels in rat sensory neurones is >1 AM (Bevan & Szolcsanyi, 1990), and this concentration accords with that utilized for the neuropeptide depletion in isolated tissues (e.g. Saito et al, 1987;Ellis & Burnstock, 1989). Saito et al (1987) reported that capsaicin reversibly inhibited part of the neurogenic contraction at 0.1 JM, but the depletion of the neurotransmitter responsible for this inhibition (presumably, calcitonin-gene-related peptide) required 1 to 10 AM of capsaicin in smooth muscle of rat vas deferens.…”

“…Capsaicin has also been shown to block neurotransmission not mediated by adrenoceptors or acetylcholine receptors in various tissues. This block of 'non-adrenergic non-cholinergic' transmission is considered to be due to neuronal excitation and stTbsequent depletion of neuropeptides such as substance P (Szolcsanyi & Bartho, 1978;Ellis & Burnstock, 1989) or calcitonin gene-related peptide (CGRP; Franco-Cereceda & Lundberg, 1985;Saito et al, 1987), which exist, presumably, in sensory neurones.…”