Capsaicin-induced stimulation of the guinea-pig atrium

1The motor effects of capsaicin on the guinea-pig distal colon have been investigated in vivo and in vitro. 2 Capsaicin (0.1-10 Ig kg-' i.v.) produced a transient relaxation which was reduced by pretreatment with capsaicin itself, atropine, hexamethonium, phentolamine or guanethidine and almost abolished by tetrodotoxin (TTX). Topically applied capsaicin produced a transient inhibition of tone and spontaneous activity prevented by topically applied TTX. 3 In isolated preparations of distal colon, capsaicin produced a transient, TTX-and atropinesensitive contraction which was followed by a depression of the contractile activity. The depressant effect was unaffected by atropine plus guanethidine but was greatly reduced by TTX, indicating activation of intramural non-adrenergic, non-cholinergic (NANC) mechanisms. The depressant effect on the first exposure to capsaicin (1 jiM) was greater than that produced by a second, third or fourth exposure.4 In preparations excised from capsaicin-pretreated animals, capsaicin (1 jM) only produced an inhibitory effect on spontaneous contractions. Desensitization did not occur to this inhibitory effect. 6 It is concluded that, in vivo, capsaicin activates inhibitory reflexes, presumably due to stimulation of primary afferent fibres. This effect involves, at least in part, activation of sympathetic nerves to this organ. The contractile effect of capsaicin on the isolated colon involves activation of intramural cholinergic neurones, whereas the TTX-sensitive component of the inhibitory effect involves either release of an inhibitory transmitter through an axon reflex arrangement or activation of NANC neurones. In addition, at high concentrations capsaicin produces a direct depression of smooth muscle contraction.

Section: Effects Of Capsaicin On the Isolated Colonmentioning

confidence: 99%

Section: Effects Of Capsaicin On the Isolated Colonmentioning

confidence: 99%

Four motor effects of capsaicin on guinea‐pig distal colon

Maggi

Meli

Santicioli

1987

“…pigs (Lundberg et al, 1984a). The physiological responses may, therefore, be due to release of neuropeptides localized to capsaicin-sensitive nerves.…”

Section: Introductionmentioning

confidence: 99%

“…Capsaicin is the major pungent principle of hot peppers of the plant genus Capsicum and has been shown to deplete primary afferent C-fibres of stored neuropeptides (Buck & Burks, 1986). Capsaicin itself causes a depolarization of afferent Cfibres which induces local effects including vasodilatation and plasma extravasation in guinea-' Author for correspondence.pigs (Lundberg et al, 1984a). The physiological responses may, therefore, be due to release of neuropeptides localized to capsaicin-sensitive nerves.…”

mentioning

confidence: 99%

Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea‐pigs

Rogers

Belvisi

Aursudkij

et al. 1988

123

1 We have studied the effect of the sensory neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) on microvascular permeability in guinea-pig airways in vivo and investigated whether CGRP would potentiate the effect of SP. We used the extravasation of intravenously-injected Evans blue dye as an index of permeability. 2 The tachykinins SP, NKA and NKB (0.025-5.Onmol kg-, i.v.) significantly (P <0.05) increased extravasation of dye in a dose-related manner and with a similar pattern of distribution; they were most potent in the trachea and main bronchi, less potent in the larynx and intrapulmonary airways, and had little significant effect in the bladder.3 SP was significantly more potent in causing extravasation of dye than NKA or NKB with ED50 values (nmol kg-1) in the range 0.04-0.1, depending on the airway level, compared with values in the range 0.3-0.7 for the neurokinins. 4 CGRP (0.0025-2.5 nmol kg-1, i.v.) had no significant effect on microvascular permeability and did not potentiate SP-induced extravasation of dye. 5 Each neuropeptide decreased mean arterial blood pressure, indicating vasodilatation, in a doserelated manner. Co-injection of CGRP and SP produced additive decreases in arterial pressure. 6 We conclude that, in guinea-pig airways, tachykinins increase microvascular permeability via tachykinin receptors of the NK-1 sub-type (indicated by an order of potency of SP > NKA = NKB) on endothelial cells. The response appears to be related to mechanisms in addition to vasodilatation. The relevance of the responses to the tachykinins in asthma is discussed. IntroductionElectrical stimulation of the cervical vagus nerves in rat and guinea-pig induces a number of physiological responses including vasodilatation and increased permeability of the microvasculature of the trachea to macromolecules (Lundberg & Saria, 1982;Lundberg et al., 1983). Both responses are preserved in the presence of atropine, hexamethonium or antihistaminic drugs, but are absent in animals pretreated with capsaicin. Capsaicin is the major pungent principle of hot peppers of the plant genus Capsicum and has been shown to deplete primary afferent C-fibres of stored neuropeptides (Buck & Burks, 1986). Capsaicin itself causes a depolarization of afferent Cfibres which induces local effects including vasodilatation and plasma extravasation in guinea-' Author for correspondence.pigs (Lundberg et al., 1984a). The physiological responses may, therefore, be due to release of neuropeptides localized to capsaicin-sensitive nerves. For example, the tachykinin substance P (SP) has been localized to sensory nerves in the airways of several species, including man (Lundberg et al., 1984b). SP and two newer members of the tachykinin family, neurokinin A (NKA) and neurokinin B (NKB) have been shown to increase vascular permeability in guinea-pig trachea (Lundberg et al., 1985) although, of the two neurokinins, only NKA has been localized to capsaisin-sensitive nerves in the guinea-pig (Hua...

“…Capsaicin has previously been shown to exert powerful, positive chronotropic and inotropic effects in isolated, spontaneously beating atria of guineapigs (Molnar et al, 1969;Lundberg et al, 1984;. The precise mechanism of these effects is still unknown, however there is evidence that the effects of capsaicin in guinea-pig hearts are mediated by CGRP released from cardiac capsaicin-sensitive sensory nerves Saito et al, 1986;1987;Franco-Cereceda et al, 1987a,b;.…”

Section: Introductionmentioning

confidence: 99%

Effects of capsaicin desensitization on the stimulatory effect of kinins, prostaglandins, biogenic amines and various drugs in guinea‐pig isolated atria

Bernoussi

Rioux

1989

1 A simple desensitization protocol was set up using capsaicin and isolated, spontaneously beating atria of guinea-pigs to assess the possible participation of cardiac, capsaicin-sensitive, substance P (SP)-and calcitonin gene-related peptide (CGRP)-containing sensory nerve fibres, in the cardiac stimulatory effects of bradykinin (Bk), kallidin (Kd), 5-hydroxytryptamine (5-HT), histamine, prostaglandin E2 (PGE2), prostaglandin El (PGE1), prostaglandin F2., (PGF2Z), adrenaline (Ad), glucagon, nicotine and angiotensin II (All). 2 The positive chronotropic and inotropic effects of Bk, Kd and 5-HT were markedly reduced in capsaicin-desensitized atria compared to control. The percentage inhibition of the chronotropic and inotropic responses to the three agonists seemed to be inversely related to the concentration of agonist used and to vary also with the type of cardiac effect produced by the drug (for Bk the percentage inhibition was: 36-81% (chronotropic effect) and 62-86% (inotropic effect); for Kd: 61-78% (chronotropic effect) and 53-77% (inotropic effect); for 5-HT: 25-66% (chronotropic effect) and 40-64% (inotropic effect)).3 The positive chronotropic and inotropic effects of histamine, PGEl, PGE2, PGF2., glucagon and AII had similar amplitudes in capsaicin-desensitized and control atria. 4 The positive chronotropic and inotropic effects of Ad and nicotine were differentially affected by capsaicin desensitization. The inotropic effects of 7.5 x 1O-' and 7.5 x 10-6M Ad were reduced by 41 and 27% respectively, in capsaicin-desensitized atria compared to control. The chronotropic effects of 1.54 x 10'-and 6.17 x 10-M nicotine were inhibited by 57 and 26% respectively, by capsaicin desensitization. On the other hand, the chronotropic effect of Ad and the inotropic action of nicotine were of similar amplitude in capsaicin-desensitized and control atria. 5 These results were taken as an indication that a substantial part of the chronotropic and inotropic effects of Bk, Kd or 5-HT in guinea-pig atria, unlike those of histamine, PGE1, PGE2 PGF2., glucagon and All, might be the result of stimulation of capsaicin-sensitive, SP-and CGRP-containing sensory nerve fibres. The slight, differential inhibition of the chronotropic and inotropic effects of Ad and nicotine by capsaicin desensitization suggests a minor contribution by cardiac, capsaicin-sensitive sensory nerve fibres to the effects of nicotine and Ad in guinea-pig atria.