Calcitonin gene-related peptide (CGRP) in capsaicin-sensitive substance P-immunoreactive sensory neurons in animals and man: Distribution and release by capsaicin

1 Endothelin-1 (ET-1), endothelin-3 (ET-3) and noradrenaline (NA) were administered as intra-arterial bolus injections into the isolated, blood-perfused spleen of the dog to assess agonist properties and relative molar potencies on the vascular and capsular smooth muscle. 2 An initial small vasodilatation was observed occasionally at low doses (1.0-i0pmol) of ET-1. 3 ET-1, ET-3 and NA all caused graded increases in splenic arterial vascular resistance. The molar ED50 for the splenic vasoconstrictor response to ET-1 was significantly less (P < 0.001) than that to ET-3; both peptides were significantly more potent as vasoconstrictor agents than NA. The maximum increase in splenic arterial vascular resistance was not significantly different for either ET-1, The time course of the splenic vasoconstrictor response to ET-1 was significantly (P < 0.01) longer than that to equieffective doses of ET-3 or NA. 5 The splenic vasoconstrictor responses to ET-1 and ET-3 were accompanied by reductions in spleen volume. The rank order of molar potency in causing splenic capsular contraction was ET-i > ET-3 > NA. The maximum reduction in splenic volume was significantly greater for NA than for either ET-i or ET-3. The two peptides (ET-1, ET-3) were equiefficacious in contracting splenic capsular smooth muscle. 6 The high molar potency of ET-1 as a splenic arterial vasoconstrictor, over 1,700 times more potent than NA, suggests that it may play an important local role in the control of splenic haemodynamics.

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The actions of endothelins−1 and −3 on the vascular and capsular smooth muscle of the isolated blood perfused spleen of the dog

Withrington

Ansari

Croxton

et al. 1992

“…Other studies have shown that chronic treatment of animals with capsaicin produces extensive depletion of primary afferents of their SP and CGRP content (Papka et al, 1981;Gibbins et al, 1985;Lundberg et al, 1985;Saito et al, 1986). Capsaicin seems to be markedly specific for SP-and CGRP-containing neurones for, in capsaicin-pretreated guinea-pigs, it causes a depletion of cardiac SP-and CGRP-containing neurones of their SP and CGRP content Saito et al, 1986;Franco-Cereceda et al, 1987a), without affecting cardiac, adrenergic and vasoactive intestinal polypeptide (VIP)-containing neurones (Papka et al, 1981;Della et al, 1983), or the functional response of guinea-pig atria to field stimulation of cardiac adrenergic nerve fibres or terminals (Saito et al, 1986;1987).…”

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.

“…Capsaicin releases SP (Gamse et al, 1979) and CGRP (Franco-Cereceda et al, 1987) from sensory nerve terminals, and SP (Johnson & Erdos, 1973) and CGRP (Piotrowski & Foreman, 1986) are known to liberate histamine from mast cells. However, the secretory response to capsaicin in the present study was not reduced by H1-or H2-receptor blockers.…”

Section: Resultsmentioning

confidence: 99%

“…Capsaicin is known to evoke the release of SP (Jessell et al, 1978) and CGRP (Franco-Cereceda et al, 1987) from such nerve fibres. SP stimulates the secretion of nasal fluid (Petersson, 1989) whereas CGRP does not (Geppetti et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Capsaicin evokes secretion of nasal fluid and depletes substance P and calcitonin gene‐related peptide from the nasal mucosa in the rat

Petersson

Malm

Ekman

et al. 1989

The secretion of nasal fluid was studied in anaesthetized rats after topical application of capsaicin, and of calcitonin gene-related peptide (CGRP) alone or CGRP in combination with substance P (SP). The flow of nasal fluid was stimulated and the secretions collected by a filter paper technique. The concentrations of SP and CGRP in nasal biopsies were determined after topical or systemic administration of capsaicin. 2 Capsaicin (single dose administration) stimulated nasal secretion in a dose-dependent manner. The effect was inhibited by hexamethonium, lignocaine, or by the tachykinin antagonist (D-Pro2, DTrp7' 9)-SP, but not by atropine, or by a combination of the histamine H -receptor antagonist chlorpheniramine and the H2-receptor antagonist ranitidine. 3 When applied cumulatively, capsaicin rapidly produced desensitization. The concentrations of SP and CGRP in the nasal mucosa were reduced by capsaicin 6 days after topical or s.c. administration but not 15 min after topical application of desensitizing doses. 4 CGRP did not stimulate the secretion of nasal fluid and did not alter SP-evoked nasal secretion. 5 The inhibition by hexamethonium of the capsaicin-evoked nasal secretion suggests the involvement of ganglionic reflexes. In addition, the inhibition of the response to capsaicin by (D-Pro2,DTrp7' 9)-SP and lidocaine and the depletion of SP and CGRP after capsaicin indicate the involvement of tachykinin-mediated axon reflexes.