Effects of substance P, cholecystokinin octapeptide, bombesin, and neurotensin on the peristaltic reflex of the guinea-pig ileum in the absence and in the presence of atropine.
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Animals↗
Biomedical subjects
J Donnerer
Publications and source records attributed to J Donnerer.
Analysis of the effects of intravenously injected capsaicin in the rat.
1. I.v. injection of 1 or 3 micrograms capsaicin led to a triphasic blood pressure response in Sprague-Dawley rats but, in contrast to Wistar rats, did not affect heart rate and respiration. The blood pressure response was a sequence of fall (A), return to normal levels or slight rise (B), and fall (C) in blood pressure. The blood pressure response to capsaicin remained unchanged after treatment with adrenoceptor or cholinoceptor antagonists. 2. The initial fall in blood pressure (A) was absent after bilateral vagotomy and in the pithed rat. The delayed fall in blood pressure (C) remained unchanged after vagotomy, but was absent after neonatal capsaicin pretreatment and in the pithed rat. Effect B was not diminished after vagotomy or despinalization: it was augmented in rats treated neonatally with capsaicin. 3. I.a. injection of capsaicin into the hind leg caused a reflex fall in blood pressure which was changed to a reflex rise in rats treated with capsaicin as neonates. 4. The initial and the delayed fall in blood pressure after i.v. injection of capsaicin seems to be reflex responses to stimulation of capsaicin-sensitive small diameter afferent fibres. The intermediate rise in blood pressure appears to result mainly from a direct short vasoconstriction by capsaicin.
Animals↗
Analgesic effect of antagonists of substance P.
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Analgesics↗
Postocclusive cutaneous vasodilatation mediated by substance P.
1. The cutaneous vasodilatation following arterial occlusion ("reactive hyperemia") was studied in the rat hind paw. A peak increase in venous outflow of 200-250% was observed within 1 min after a 3 min occlusion period. 2. Chronic denervation as well as capsaicin pretreatment reduced the postocclusive cutaneous vasodilatation by more than 60% (P less than 0.01). This demonstrates that the reactive vasodilatation is of neurogenic origin and mediated by small diameter afferent fibres. 3. Reduction of the postocclusive cutaneous vasodilatation after histamine depletion by compound 48/80 indicates the involvement of histamine. 4. Among all neuropeptides known to occur in primary sensory neurones only substance P and vasoactive intestinal polypeptide cause vasodilatation when infused i.a. into the rat paw. In contrast to antidromic sensory nerve stimulation or i.a. substance P infusion, vasoactive intestinal polypeptide does not cause plasma extravasation. The vasodilator potency of vasoactive intestinal polypeptide is about 1/500 of substance P in the rat paw. Therefore only substance P is able to mimic the reactive vasodilatation. 5. It is concluded that the postocclusive cutaneous vasodilatation is caused mainly by the release of substance P from peripheral endings of small diameter nerve fibres. The "axon reflex", also involving neurogenic vasodilatation, is assumed to be exerted by the same mechanism.
Animals↗
Time course of capsaicin-induced functional impairments in comparison with changes in neuronal substance P content.
1. Changes in the content of substance P (dorsal spinal cord, dorsal roots, dorsal root ganglia, saphenous nerve, skin) and functional changes (neurogenic plasma extravasation, chemosensitivity of the cornea) were measured in the rat from 10 min to 4 days after the s.c. injection of a single dose of 50 mg kg-1 capsaicin. 2. The substance P content in dorsal roots, saphenous nerve and hind paw skin progressively declined to about 60--70% of control 4 days after treatment, whereas that of the dorsal root ganglia rose, after an initial decline, to 140% after 1--4 days. 3. After denervation, impairment of neurogenic plasma extravasation could be observed not earlier than after one day, thus being comparable in time course to the depletion of substance P in the skin and saphenous nerve. 4. Neurogenic plasma extravasation and the chemosensitivity of the cornea were greatly diminished already 10 min after systemic capsaicin treatment, i.e. at a time when the substance P content of the peripheral nerve was still unchanged. These early effects of systemic capsaicin treatment are therefore caused by actions other than depletion of substance P.
Animals↗
Release of histamine by substance P.
1. The basic peptide substance P causes histamine release from peritoneal mast cells of the rat in vitro whereas the closely related neutral peptides eledoisin and physalaemin do not. 2. Infusion of substance P (7.4 nmol min-1), but not of eledoisin (8.4 nmol min-1) or physalaemin (7.9 nmol min-1), into the rat hindquarter preparation caused a more than 4-fold increase of the histamine content in the venous outflow. The outflow of 5-HT remained unchanged under infusion of all three peptides. 3. No histamine depletion in the skin of the rat hind paw was observed following antidromic stimulation of the saphenous nerve or cutaneous application of mustard oil. Infusion of substance P (7.4 nmol min-1) caused a 47% depletion of histamine in the paw skin although only a small proportion of the infused substance P seemed to enter the tissue from the blood vessels. 4. The results further substantiate the view that substance P upon release from peripheral nerve endings induces release of histamine from cutaneous mast cells, a mechanism which contributes to neurogenic vasodilatation and plasma extravasation.
Animals↗
Caerulein, substance P, serotonin and cholinomimetics induce rhythmic contractions of the intestinal circular muscle.
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Animals↗
Activation of primary afferent neurons by thermal stimulation. Influence of ruthenium red.
The effect of thermal stimulation on primary afferent neurons and its modulation by Ruthenium Red (RR) has been investigated in the isolated perfused rabbit ear with intact neuronal connection to the animal. Capsaicin, K(+)-depolarization as well as increasing the temperature of the perfusate to 50 degrees C, increased the amount of substance P-like immunoreactivity (SP-IR) in the outflow in a calcium-dependent manner. High performance liquid chromatography (HPLC) revealed that SP-IR which was released by thermal stimulation consisted of two components, one of which co-eluted with synthetic substance P. The same two components of SP-IR were also present in extracts of the auricular nerve and were released by capsaicin. RR attenuated the effect of capsaicin and thermal stimulation but did not reduce potassium-evoked release of SP-IR. To evaluate an inhibitory action of RR on the excitation of primary afferents, the isolated perfused ear with intact neuronal connection to the anaesthetized rabbit was used. Intraarterial injection of capsaicin or bradykinin as well as superfusion of a skin area of approximately 2 cm2 with water at 53 degrees C for 1 min, produced a depressor reflex. RR attenuated the response to thermal stimulation and to capsaicin, but did not block the bradykinin-induced depressor reflex. These results demonstrate that, in the rabbit ear, thermal stimuli excite primary afferent neurons and evoke the calcium-dependent release of neuropeptides from their peripheral terminals by a mechanism which is sensitive to RR.
Animals↗