Galanin: a potent modulator of excitatory neurotransmission in the human urinary bladder.

Galanin (GAL) produced a concentration (0.3-100 nM)-related inhibition of the atropine-sensitive component of the contractions induced by field stimulation of detrusor strips from the dome of the human urinary bladder. GAL had an ED50 of 2 nM for the inhibition.

Synthesis and biological activity of N-methylated analogues of neurokinin A.

Limited conformational constraints have been introduced in the sequence of the C-terminal heptapeptide NKA(4-10) by N-methylation of individual peptide bonds and the biological activities of the peptides thus obtained were evaluated on three in vitro preparations sensitive and quite selective for each of the naturally-occurring neurokinins, in order to assess the effect of N-methylation on receptor selectivity. The analogue methylated in position 7, namely [MeVal7] NKA(4-10) shows some selectivity for the NK-P receptor, while none of the tested compounds appear to be selective for the NK-A receptor.

Species-related variations in the effects of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity.

1. The effect of capsaicin on bladder motility in vivo (urethane anaesthesia) and in vitro, plasma extravasation (Evans blue leakage technique) and content of substance P-like immunoreactivity (SP-LI) of the urinary bladder was investigated in various mammalian species. 2.

Cutaneous lesions in capsaicin-pretreated rats. A trophic role of capsaicin-sensitive afferents?

1. The time course and regional distribution of 'spontaneous' cutaneous lesions in rats desensitized to capsaicin as newborns was correlated to behavioural observations and regional distribution of substance P-like immunoreactivity (SP-LI) and tachykinin-like immunoreactivity (TK-LI) in various skin areas. 2.

Exposure to calcium-free medium protects sensory fibers by capsaicin desensitization.

Capsaicin (1 microM) produces a tetrodotoxin-resistant contraction of the rat isolated urinary bladder ascribable to neuropeptide release from sensory nerves. A second application of capsaicin (1-10 microM) up to 5 h from the first one was ineffective, indicating complete desensitization. However, if the first exposure to capsaicin was made after a prolonged incubation in a Ca-free medium containing EDTA (0.

Capsaicin-induced inhibition of motility of the rat isolated vas deferens: do multiple neuropeptides mediate the visceromotor effects of capsaicin?

1 The effects of capsaicin have been investigated in the field-stimulated (0.1 Hz) or unstimulated rat isolated vas deferens and compared with those of some neuropeptides (neurokinins, calcitonin gene-related peptide (CGRP) putatively stored in capsaicin-sensitive sensory fibres. 2 Capsaicin (0.

Substance P-like immunoreactivity in capsaicin-sensitive structures of the rat thymus.

Unlike in mouse and hamster, the thymus of rats or guinea pigs contains measurable amounts of substance P-like immunoreactivity (SP-LI), which, in a HPLC system, eluted as authentic SP or SP sulfoxide. Ontogenetic study showed that in rats the SP-LI content of the thymus increased up to 60 days from birth, and decreased thereafter. Capsaicin, but not 6-hydroxydopamine (6-OHDA) pretreatment completely depleted thymic SP-LI content in both newborn and adult rats.

Distribution of capsaicin-sensitive urinary bladder afferents in the rat spinal cord.

The capsaicin-sensitive afferent innervation of the urinary bladder and the central nervous system distribution of urinary bladder afferents have been studied in the rat. Capsaicin-sensitive primary sensory neurones supplying the urinary bladder have been found in two groups of spinal ganglia located in the Th13-L2 and L6-S1 segments. Capsaicin-sensitive primary sensory afferents from the bladder terminate within Rexed's laminae I, V and X, and in the dorsal gray commissure of the lumbosacral spinal cord.

The effects of baclofen on spinal and supraspinal micturition reflexes in rats.

1. The effect of (+/-)-baclofen on micturition reflexes was investigated in urethane-anaesthetized rats. A 'low' dose of (+/-)-baclofen (0.

The presence of mucosa reduces the contractile response of the guinea-pig urinary bladder to substance P.

The contractile response to substance P in-vitro is greater in strips of guinea-pig bladder freed of mucosa than in normal strips, while the response to field stimulation, histamine or KCl is unaffected by the presence of mucosa. Substance P has no inhibitory effect on histamine-induced contractions of the guinea-pig bladder. These findings support the possibility that the presence of mucosa may reduce accessibility of substance P to the muscle layer.

Immunoblockade of response to capsaicin in the rat vas deferens: evidence for the involvement of endogenous calcitonin gene-related peptide.

In the rat isolated vas deferens, capsaicin induced a transitory inhibition of the nerve-mediated contractions. This effect was not observed in preparations excised from capsaicin-pretreated rats nor following a first exposure to a high concentration of capsaicin in vitro. Exogenous calcitonin gene-related peptide (CGRP) induced a concentration-related inhibition of the nerve-mediated contractions.

The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons.

In acute spinal rats (C2-C3) the transvesical infusion of saline activates a vesico-vesical excitatory reflex (Brain Res., 380 (1986) 83-93). In bladders containing a subthreshold amount of fluid the topical application of capsaicin on the outer surface of the bladder dome activated this spinal reflex and also produced a transient rise in blood pressure and heart rate.

Capsaicin-sensitive mechanisms and experimentally induced duodenal ulcers in rats.

The incidence and degree of cysteamine- or dulcerozine-induced duodenal ulcers are increased by systemic capsaicin desensitization (50 mg kg-1 s.c. 4 days before) in adult rats.

Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract.

The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra.

The correlation between sensory-efferent functions mediated by the capsaicin-sensitive neurons and substance P content of the rat urinary bladder.

The substance P-like immunoreactivity (SP-LI) of the urinary bladder of adult rats was depleted by capsaicin desensitization (50 mg/kg, s.c., 4 days before) or extrinsic denervation (pelvic ganglionectomy) thus indicating its neurogenic sensory origin.

Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy.

The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of 'in vivo' cystometry and 'in vitro' recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. After 7-9 weeks from STZ injection there was a marked increase in weight of bladder and ureters.

Further studies on the mechanisms of the tachykinin-induced activation of micturition reflex in rats: evidence for the involvement of the capsaicin-sensitive bladder mechanoreceptors.

The relative ability of substance P, neurokinin A, neurokinin B and kassinin to activate the micturition reflex was investigated in urethane-anaesthetized rats. When administered topically neurokinin A, neurokinin B and kassinin were 14, 36 and 280 times, respectively, more potent than substance P to activate micturition. On the other hand substance P, neurokinin A and kassinin were practically equipotent (and neurokinin B was about 3-4 times less potent than substance P) to stimulate the contraction of the rat isolated bladder and to potentiate the contractions induced by electrical field stimulation.

Four motor effects of capsaicin on guinea-pig distal colon.

The motor effects of capsaicin on the guinea-pig distal colon have been investigated in vivo and in vitro. Capsaicin (0.1-10 micrograms kg-1 i.

Contribution of neurogenic and myogenic factors in the response of rat proximal colon to distension.

The response of the rat proximal colon to distension and drugs that interfere with intrinsic and extrinsic nerves was investigated in vivo (urethan anesthesia) and in vitro. Saline distension induced the appearance of a cyclic contractile activity that was slightly inhibited by atropine (ATRO) and enhanced by physostigmine. Hexamethonium increased the distension-induced motor activity.

Involvement of capsaicin-sensitive mechanism(s) in the antiulcer defence of intestinal mucosa in rats.

Capsaicin desensitization increases degree and incidence of indomethacin-induced intestinal ulcers in rats, suggesting the existence of a capsaicin-sensitive mechanism(s) in the protection of the intestinal mucosa against indomethacin-induced ulceration. Sensory innervation thus may be involved in the pathogenesis of ulcers of the small bowel, as well as in gastric ulcers. Administration of exogenous CGRP and somatostatin, sensory neuropeptides which are depleted by capsaicin desensitization, does not afford protection toward the capsaicin-induced aggravation of intestinal ulcers.

Spinal and supraspinal components of GABAergic inhibition of the micturition reflex in rats.

The effect of gamma-aminobutyric acid (GABA)ergic drugs on micturition reflexes was investigated in urethane-anesthetized rats. Intracisternally administered GABA or homotaurine inhibited, in a bicuculline-sensitive manner, the supraspinal micturition reflex. Bicuculline or picrotoxin increased the amplitude and duration of the micturition contractions of supraspinal origin, suggesting the existence of a tonic GABAergic inhibitory mechanism.

Peripheral effects of neurokinins: functional evidence for the existence of multiple receptors.

The ability of six neurokinins (substance P, neurokinin A, neurokinin B, physalaemin, eledoisin and kassinin) to induce hypotension, salivary secretion and to activate motility of the duodenum and of the urinary bladder was investigated in urethane-anaesthetized rats. A comparison of the relative potency of these substances in producing a given biological effect yielded results consistent with the hypothesis of the existence of three distinct types of receptor in rat peripheral tissues, namely SP-P, SP-K and SP-E according to the nomenclature proposed by Buck, Burcher, Shults, Lovenberg & O'Donohue (1984), or NK-P, NK-A and NK-B according to that of Regoli, D'Orleans-Juste, Drapeau, Dion & Escher (1985). An NK-P receptor is responsible for the production of the hypotensive effect and for the activation of salivary secretion.