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Echinacea purpurea(L.) Moench and Hypericum perforatum(L.) were evaluated for their anti‐inflammatory activity against carrageenan‐induced paw oedema in mice. Each drug was administered orally to mice at 30 and 100 mg kg−1, twice daily. Only the higher dose significantly inhibited, time dependently, the formation of oedema, evaluated as area under the curve (echinacea P< 0.01; hypericum P< 0.05). Western blot analysis showed that in‐vivo treatment with these extracts could modulate lipopolysaccharide (LPS) and interferon‐γ induced cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) expression in peritoneal macrophages. In particular, treatment with 100 mg kg−1hypericum inhibited both iNOS and COX‐2 expression, whereas treatment with 100 mg kg−1echinacea down‐regulated only COX‐2 expression. The present study suggests that the anti‐inflammatory effect of these extracts could be in part related to their modulation of COX‐2 expression.

Echinacea purpurea(L.) Moench and Hypericum perforatum(L.) were evaluated for their anti-inflammatory activity against carrageenan-induced paw oedema in mice. Each drug was administered orally to mice at 30 and 100 mg kg−1, twice daily. Only the higher dose significantly inhibited, time dependently, the formation of oedema, evaluated as area under the curve (echinacea P< 0.01; hypericum P< 0.05). Western blot analysis showed that in-vivo treatment with these extracts could modulate lipopolysaccharide (LPS) and interferon-γ induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in peritoneal macrophages. In particular, treatment with 100 mg kg−1hypericum inhibited both iNOS and COX-2 expression, whereas treatment with 100 mg kg−1echinacea down-regulated only COX-2 expression. The present study suggests that the anti-inflammatory effect of these extracts could be in part related to their modulation of COX-2 expression.

Capsaicin (0.03–3 μm) induces contractions of the rat isolated bladder which are unaffected by either atropine (3 μm) or tetrodotoxin (0.5 μm). In the presence of capsaicin (0.1 μm) an enhancement of field stimulation-induced contractions was observed. Capsaicindesensitization did not modify the height of these. The neurogenic nature of the capsaicin-induced contractions was proved by the observation that ‘chronic’ (48 h) denervation prevented, while ‘acute’ (2 h) denervation did not modify the effect of capsaicin. Denervated bladders maintained their responsiveness to acetylcholine but not to field stimulation. Isolated bladders from rat pups (1–2 days old) did not respond to capsaicin while strong contractile responses to acetylcholine or field stimulation were obtained in these preparations. In bladders from two week old animals, capsaicin produced similar contractions to those observed in preparations from adult animals. The bladders from rats receiving a high dose of capsaicin (50 mg kg−1s.c.) at birth were heavier than those of their age-matched, vehicle-treated controls. Isolated bladders from 2 month old animals pretreated with capsaicin at birth were unresponsive to capsaicin while responsiveness to acetylcholine, substance P or field stimulation was unaffected compared with that of vehicle-treated controls. These experiments provide evidence that a capsaicin-sensitive innervation exists in the rat urinary bladder which undergoes a postnatal development at end organ level.

The D-2 agonist LY 171555 (0.05, 0.1, 0.2 mg kg−1s.c.) but not the D-1 agonist SK&F 38393 (5, 10, 20 mg kg−1s.c.) reduced reserpine-induced hypothermia (RIH) in mice. This effect was antagonized by the D-2 antagonist (-)-sulpiride (50 mg kg−1i.p.) but not by the D-1 antagonist SCH 23390 (0.1 mg kg−1s.c). SK&F 38393 (20 and 1 mg kg−1s.c.) did not alter the effect of LY 171555 (0.1 and 0.2 mg kg−1) on RIH, but administration of both LY 171555 (0.2 mg kg−1s.c.) and SK&F 38393 (1 mg kg−1s.c.) antagonized the reserpine-induced sedation.

The effects of some vasodilators on the mobilization of different Ca2+pools during contractions produced by noradrenaline and high K+medium in rabbit ear artery has been investigated. Sodium nitrite was much more effective in antagonizing high K+-stimulated Ca2+fluxes through the potential-dependent Ca2+channels than noradrenaline-induced mobilization of intracellular Ca2+stores or Ca2+fluxes through receptor-operated channels. Papaverine was only slightly more active on contractions sustained by influx of extracellular Ca2+(through potential-dependent channels and receptor-operated channels) than on those sustained by intracellular Ca2+. Verapamil and nifedipine were much more effective in antagonizing contractions sustained by Ca2+entry through potential-dependent channels than through receptor-operated channels. Nifedipine was completely ineffective in antagonizing noradrenaline-induced mobilization of intracellular Ca2+stores while verapamil had a limited inhibitory action in high concentrations. Phentolamine was equieffective in antagonizing both types of noradrenaline-induced contractions while having no effect on high K+-induced tonic contraction.

The effects of GABA and selective GABAAand GABABreceptor agonists and antagonists have been investigated on field stimulation-induced contractions (0·1 Hz) of rabbit urinary bladder strips in-vitro. Atropine inhibits twitches of bladder strips obtained from the bladder dome more effectively than those obtained from the bladder base. Both GABA and the selective GABABreceptor agonist, (±)-baclofen inhibited field stimulation-induced contractions to about the same extent, while the selective GABAAreceptor agonist, homotaurine had no effect. In the presence of atropine, GABA failed to inhibit further the amplitude of twitches. The effects of either GABA or (±)-baclofen were antagonized by the GABABreceptor antagonists homotaurine and 5−aminovaleric acid, while the GABAAreceptor antagonist picrotoxin had no effect. Neither GABA nor (±)-baclofen had any significant effect on acetylcholine-induced contractions of unstimulated bladder strips, but they were abolished by atropine. These results suggest that GABABreceptors inhibit field stimulation-induced contractions of rabbit bladder muscle by reducing the amount of acetylcholine released per nerve impulse.

The mobilization of cellular and extracellular Ca2+pools by selective α1-adrenoceptor (phenylephrine) and α2-adrenoceptor (xylazine) agonists as well as noradrenaline was evaluated in rabbit ear artery. Noradrenaline and phenylephrine possess full instrinsic activity for both types of Ca2+mobilization whereas xylazine up to 1 mM had only a limited contractile effect, being more effective in inducing extracellular Ca2+-dependent response. However, extracellular Ca2+was mobilized by xylazine in a concentration 20 times higher than that required to stimulate pre-junctional α2-adrenoceptors. Noradrenaline (5 μM) and xylazine (1 mM) induced cellular and extracellular Ca2+-dependent contractions which were prazosin-sensitive and yohimbine-resistant. Xylazine-induced contractile activity, particularly that dependent upon the extracellular Ca2+pool, was markedly reduced by selective adrenergic denervation with 6-hydroxydopamine, but the actions of noradrenaline were unaffected. These results suggest that: (1) rabbit ear artery contain post-junctional α1-adrenoceptor but not α2-adrenoceptors; (2) stimulation of these α1-adrenoceptors can account for the overall contractile activity of exogenously added noradrenaline and (3) stimulation of α1-adrenoceptors results in mobilization of cellular as well as extracellular Ca2+pools.

Intracisternal glycine, but not GABA, activates a series of neurogenic rhythmic contractions of the urinary bladder in urethane-anaesthetized rats. This effect of glycine was prevented by strychnine but not by bicuculline, indicating the involvement of specific glycinergic receptors. The effects of glycine were also prevented by either atropine or haloperidol suggesting an involvement of cholinergic and monoaminergic excitatory neurotransmission to the bladder.

The reversal of hypothermia, induced by reserpine or by a high (16 mg) dose of apomorphine, in male Swiss mice, does not seem to utilize a common mechanism. Desipramine (20 mg kg−1i.p., 60 min) or nortriptyline (8 mg kg−1i.p., 60 min) increased temperature in both reserpine (2.5 mg kg−1s.c, 18–19 h) and apomorphine (16 mg kg−1s.c, 30 min) treated mice. In apomorphine-treated animals the effect of both drugs was reversed by the mixed dopaminergic D1- D2-antagonist haloperidol (1 mg kg−i.p 90 min), the D1-receptor blocking drug SCH 23390 (0.05 mg kg−1s.c, 30 min), the ?1-adrenoceptor blocking drugs prazosin (3 mg kgsp>−1s.c., 90 min) and phenoxybenzamine (20 mg kg−1i.p., 65 min), the ?-adrenoceptor blocking drug (±)-propranolol (10 mg kg−1i.p., 120 min), and the opioid antagonist naloxone (2 mg kg−1i.p., 15 min). In contrast the selective D2-antagonist (±)-sulpiride (100 mg kg−1i.p., 90 min), and the ?2-antagonist yohimbine (2 mg kg−1i.p., 75 min), failed to effect the reversal of apomorphine hypothermia brought about by desipramine or nortriptyline. Their temperature effects in reserpinized mice were not modified by any of the antagonists tested.

Cotton pellet-induced granuloma formation in intact animals is intimately dependent upon body growth and general anabolic processes. Deposition of connective tissue around the pellet continues up to (and probably beyond) the observation period of 90 days after implantation. Anorexic or catabolic agents, or both, or restricted food intake markedly impairs granuloma formation as a result of an impaired body growth. By expressing the amount of granuloma formed in mg/100 g body weight, the true anti-granulomatous properties of a drug can be easily dissociated from those attributable to an impaired body growth. The mechanism by which impairment in body growth affects granuloma formation is discussed.

Intravenous GABA inhibited, in a bicuculline-sensitive manner, contractions of the urinary bladder induced by preganglionic nerve stimulation in urethane anaesthetized rats, while it had no significant effect on contractions produced by postganglionic nerve stimulation. In addition, intravenous GABA strongly inhibited DMPP-induced bladder contractions; this effect was also prevented by bicuculline. These experiments suggest that GABA inhibits excitatory neurotransmission in rat pelvic ganglia through a mechanism involving, at least in part, the activation of postsynaptic GABA A receptors.

Levamisole, in doses similar to those required to observe immunostimulation in animals, antagonized dose−dependently, in rats, gastric ulcers produced by necrotizing agents (HCl and ethanol) and NSAIDs (indomethacin and piroxicam) without affecting the anti−inflammatory properties of these latter drugs.

The incidence and degree of cysteamine- or dulcerozine-induced duodenal ulcers are increased by systemic capsaicin desensitization (50 mg kg−1s.c. 4 days before) in adult rats. Acute administration of capsaicin, but not neurokinins or CGRP, produced a small but distinct plasma extravasation (Evans blue leakage) in the rat proximal duodenum which was absent in capsaicin-pretreated rats. These findings indicate the existence of a capsaicin-sensitive ‘duodenal defence mechanism’ in rats.

The laxative effect of senna has been investigated in normal and essential fatty acid deficient (EFAD) rats. Oral administration of senna pod extract (7-5-90 mg kg−1) produced a dose-dependent increase in the number of soft faeces excreted by normal rats. Senna 30 mg kg−1also reversed net absorption of water and increased the prostaglandin (PG) production in the colonic lumen of normal rats by about four times. Oral administration of senna pod extract to rats, maintained on a fat-free diet for 30–90 days, produced diarrhoea and reversed net absorption of water as in normal rats. However, a fat-free diet reduced the PG production drastically in the colonic lumen both in senna-free rats and in senna-treated rats. In EFAD rats carrageenan oedema, but not dextran oedema, was also drastically reduced. Since PG mediation is not present in EFAD rats we conclude that the PG are not essential for laxation induced by senna and that water secretion and PG production in the rat intestinal lumen are unrelated.

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.

[pro4, trp7,9, Leu11]SP-(4−11), a substance P(SP) antagonist, selectively antagonized contractions produced by either capsaicin or SP on the rat isolated urinary bladder. These experiments provide direct evidence indicating that the motor effects of capsaicin on rat urinary bladder are attributable, at least in part, to the release of endogenous SP.

Systemic capsaicin pretreatment worsens trinitrobenzene sulphonic acid-induced colitis but has no effect on colitis induced by ethanol or acetic acid. The influence of capsaicin-sensitive fibres on experimentally-induced colitis seems to depend upon the type of ulcerogenic stimuli in relation to its chronic nature.

The antinociceptive effect of subcutaneous 4,5,6,7-tetrahydroisoxazol[5,4-c]pyridin-3-ol (THIP) or (±)-baclofen, measured as reaction time of rats placed on a plate heated to 55 °C, was assessed after a single or the last repeated (18 consecutive days) dose (5 mg kg−1once daily) of subcutaneous desipramine. Baclofen (10 mg kg−1)-induced antinociception was reduced by acute and unaffected by chronic desipramine treatment. On the contrary, THIP (20 mg kg−1)-induced antinociception was unaffected by acute and reduced by chronic desipramine.