Degranulation of the mast cell has been reported by the injection of histamine liberators and other chemical agents. Chlorpheniramine maleate (1.2mg./kg. and 0.3mg./kg. comprising 1/74and 1/290 of LD50 respectively), which is an antihistamine agent, in physiological saline solution for intravenous injection and in Tyrode solution for intraperitoneal injection were given in single dose. The mesenteric mast cells stained in Pugh solution, as applied by Lee (1968), were counted according to the classification of An (1964) in 4 types; the typical normal mast cell, the Grade I type of mast cell, the Grade II type of mast cell and the Grade III type of mast cell. In the experimental rats given 1.2mg./kg. of chlorpheniramine intravenously, more mesenteric mast cells were s1ightly degranulated than those cells of the rats given 0.3mg./kg. of chlorpheniramine and the control rats. In the experimental rats given 1.2mg./kg. and 0.3 mg./kg. of chlorpheniramine intraperitoneally, more mesenteric mast cells were slightly degranulated than those cells of the control rats. However, in this intraperitoneal study the degree, or severity, of degranulation of the mesenteric mast cell was not in direct proportion to the dosage of this antihistamine. Consequently it is deduced that the experimental dosage of the antihistamine chlorpheniramine maleate, applied 1/74 and l/290 of LD50, caused an evient degranulation of mesenteric mast cells of the albino rats associated with probable histamine liberation.
Animal ; Chlorpheniramine/pharmacology ; Cytoplasmic Granules* ; Female ; Histamine H1 Antagonists/pharmacology* ; Male ; Mast Cells/drug effects* ; Rats

The carotid sinus baroreceptor reflex (CSR) is an important approach for regulating arterial blood pressure homeostasis instantaneously and physiologically. Activation of the central histaminergic or cholinergic systems results in CSR functional inhibitory resetting. However, it is unclear whether two systems at the nucleus tractus solitarius (NTS) level display cross interaction to regulate the CSR or not. In the present study, the left or right carotid sinus region was isolated from the systemic circulation in Sprague-Dawley rats (sinus nerve was reserved) anesthetized with pentobarbital sodium. Respective intubation was conducted into one side isolated carotid sinus and into the femoral artery for recording the intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) simultaneously with pressure transducers connection in vivo. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner (40 mmHg) which was added at every step for over 4 s, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the precondition of no influence on the basic levels of the artery blood pressure, the effects and potential regulatory mechanism of preceding microinjection with different cholinoceptor antagonists, the selective cholinergic M1 receptor antagonist, i.e., pirenzepine (PRZ), the M2 receptor antagonist, i.e., methoctramine (MTR) or the N1 receptor antagonist, i.e., hexamethonium (HEX) into the NTS on the changes in function of CSR induced by intracerebroventricular injection (i.c.v.) of histamine (HA) in rats were observed. Meanwhile, the actions and possible modulatory mechanism of preceding microinjection with different histaminergic receptor antagonists, the selective histaminergic H1 receptor antagonist, i.e., chlorpheniramine (CHL) or the H2 receptor antagonist, i.e., cimetidine (CIM) into the NTS on the changes in function of CSR resulted from the i.c.v. cholinesterase inhibitor, physostigmine (PHY) were also examined in order to confirm and to analyze effects of cross interaction between central histaminergic and cholinergic systems on CSR. The main results obtained are as follows. (1) Standalone microinjection of different selective cholinergic receptor antagonists (PRZ, MTR or HEX) or different selective histaminergic receptor antagonists (CHL or CIM) into the NTS with each given dose had no effects on the CSR function and on the basic levels of the artery blood pressure, respectively (P > 0.05). (2) The pretreatment of PRZ or MTR into the NTS with each corresponding dose could attenuate CSR resetting resulted from i.c.v. HA in some degrees, which remarkably moved the posterior half range of ISP-MAP relationship curve downwards (P < 0.05), shifted the middle part of ISP-Gain relationship curve upwards (P < 0.05), and increased reflex parameters such as the MAP range and maximum gain (P < 0.05), but decreased parameters such as saturation pressure and intracarotid sinus pressure at maximum gain (P < 0.05). The catabatic effects of pretreatment with MTR into the NTS on CSR resetting induced by i.c.v. HA were more obvious than those with PRZ (P < 0.05), but pretreatment of HEX with given dose into the NTS had no effects on CSR resetting induced by i.c.v. HA (P > 0.05). (3) The effects of pretreatment of CHL or CIM into the NTS with each corresponding dose on CSR resetting made by i.c.v. PHY were similar to those of pretreatment of PRZ or MTR into the NTS on CSR resetting resulted from i.c.v. HA, and the decreasing effects of pretreatment with CHL into the NTS on CSR resetting induced by i.c.v. PHY were more remarkable than those with CIM (P < 0.05). These findings suggest that CSR resetting resulted from either HA or PHY into the lateral ventricle may partly involve the descending histaminergic or cholinergic pathway from the hypothalamus to NTS, which might evoke a cross activation of the cholinergic system in the NTS, via cholinergic M1 and M2 receptors mediation, especially the M2 receptors showing actions, or trigger another cross activation of the histaminergic system in the NTS, by histaminergic H1 and H2 receptors mediation, especially the H1 receptors displaying effects.
Animals ; Baroreflex ; Carotid Sinus ; physiology ; Chlorpheniramine ; pharmacology ; Cholinergic Antagonists ; pharmacology ; Cimetidine ; pharmacology ; Histamine ; pharmacology ; Pressoreceptors ; physiology ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus ; physiology

OBJECTIVETo study the pharmacologic characteristics in synergism and complementation of 999 Ganmaoling (GML), a compound recipe composed of Chinese and Western materia medica (CMM & WMM), as well as its theoretical basis of matching of Chinese and Western materia medica.

METHODSThe torsion response induced by glacial acetic acid in mice, toe swelling induced by carrageenanin rats, delayed hypersensitive response in mice and fever induced by endotoxin in rats and rabbits were used to comparatively study the actions of CMM & WMM in GML. The effect of CMM in antagonizing liver damage caused by WD (acetaminophen) in mice was also studied. RT-PCR method was used to analyze the expression of related cytokines.

RESULTSGML showed a significant antipyretic and analgesic effect, it could inhibit the carrageenan induced inflammation, antagonize the endotoxin induced fever, and promote the amount for expression of cytokines in rats' splenic tissue with pneumococci infection to some extent. The CMM in GML showed certain protective effect on acetaminophen induced liver damage.

CONCLUSIONGML has a potent antipyretic, analgesic and anti-inflammatory effects, CMM & WMM in GML showed markedly synergism and complementation, and CMM in it has liver protective effect.

Acetaminophen ; pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Caffeine ; pharmacology ; Chlorpheniramine ; pharmacology ; Common Cold ; drug therapy ; Drug Combinations ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Rabbits ; Rats ; Rats, Sprague-Dawley

To determine the effect of stress on carotid sinus baroreceptor reflex (CSR) and whether or not central histaminergic receptors modulate the CSR under stress, the characteristics of CSR were analyzed by using an isolated carotid sinus preparation in Wistar rats. Animals were divided into two groups at random: unstressed group (n=42) and stressed group (n=41). According to the site of microinjection of histaminergic receptor antagonists, each group was subdivided into a group of intracerebroventricular injection (i.c.v.) and a group of microinjection into the nucleus of the solitary tract (NTS). The volume of injection into the lateral cerebroventricle and NTS was 5 microl and 1 micro1, respectively. Stressed groups were subjected to unavoidable electric foot-shock twice daily for a week, each session of foot-shock lasted 2 hours. The left and right carotid sinus regions were isolated from the systemic circulation under anesthesia with pentobarbital sodium in all rats. The intracarotid sinus pressure (ISP) was altered in a stepwise manner to trigger CSR from 0 to 280 mmHg at every step of 40 mmHg and 4 s, and then returned to 0 mmHg in similar steps. ISP and mean arterial pressure (MAP) were recorded simultaneously. ISP-MAP relationship curve was constructed by fitting to the logistic function with five parameters. The CSR parameters and the ISP-MAP relationship curve were separately compared statistically. The main results obtained are as follows. (1) Stress significantly shifted the ISP-MAP relationship curve upwards and obviously moved the middle part of ISP-Gain relationship curve downwards, and decreased the value of the MAP range and maximum gain (G(max)), but increased the threshold pressure (TP), saturation pressure (SP), set point and ISP at G(max) (ISP(Gmax)). (2) I.c.v. of H1 receptor antagonist chlorpheniramine (CHL, 5 microg) or H2 receptor antagonist cimetidine (CIM, 15 g) significantly diminished the above-mentioned changes in CSR performance induced by stress; the alleviative effect of CIM was less remarkable than that of CHL. The responses of CSR in stressed rats to H(1) or H(2) receptor antagonists generally occurred 20 min after the administration and lasted approximately for 15 min. (3) After microinjection of CHL (0.5 microg) or CIM (1.5 microg) into the NTS, the responses of CSR in stressed groups were similar to those after i.c.v. injection of CHL or CIM. (4) However, microinjection of CHL or CIM into the lateral cerebroventricle or the NTS could not completely abolish the stress-induced changes in CSR. These findings suggest that stress results in a resetting of CSR, a decrease in reflex sensitivity. The stress-induced changes in CSR may be mediated, at least in part, by activating the brain histaminergic system. The central histaminergic receptors (H(1) and H(2) receptors) may play an important role in the resetting of CSR under stress. The descending histaminergic pathway from the hypothalamus to NTS may be involved in these effects.
Animals ; Baroreflex ; drug effects ; physiology ; Brain ; metabolism ; physiology ; Carotid Sinus ; physiology ; Chlorpheniramine ; pharmacology ; Cimetidine ; pharmacology ; Histamine Antagonists ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Histamine ; physiology ; Stress, Physiological ; physiology

Alcohol beverages have been used since the dawm of history and the pharmacology of alcohol has been studied extensively and the question whether alcohol is a stimulant has long been debated. now there seems little couble that alcohol is a primarys and continuous depressant of the CNS, and the general pharmacologic action of alcohol on the body is one of depression. The effects of various concentrations and type of alcoholic beverages on the gastrointestinal motor and secretory functions are influenced by a number of factors such as the state by the digestive processes, the presence or absence or gastrointestinal diseases, the amount and type of food present, the degree of tolerance for alcohol, accompanying psychological factiors, and so forth. it is generally accepted that gastirc secretion is stimulated by ehanol, but effects of ethanol on the motility of the gastrointestinal tract has not been clarified yet. Hence the present study was undertaken to investigate the effects of ethanol on gastrointestinal motility. The rabbits of either sex, weighting about 2kg, were killed by air embolism after 72 hours deprivation of food except water. The stomach and duodenum were isolated and cut into two parts, i.e. antrum and duodenum. Each strip of antrum and duodenum, sized 0.5X2.0cm, was placed in temperature controlled uscle chamber(37 degrees C) Containing Tyrode's solution and its contractile movement was recorded on Grass Polygraph(Model 7) via force displacement transducer(FT.03). The results are summarized as follows: 1) The strips of gastric antrum and duodenum showed spontaneous regular movement through the experimental period. Administration of ethanol from 0.1 to 1.0% inhibited the amplitude and frequency of both strips with dose-dependent manner. Most strips of the duodenum and 6 strips of the antrum showed relaxations of tone by ethanol and 4 strips of the antrum showed increased tone. 2) Tonic contraction of antral strips by ethanol was abolished only by the combined pretreatment of atropine and chlorpheniramine, or atropine and cimetidine, not by the phentolamine, proproanolol, atropine, hexamethonium, chlorpheniramine or cimetidine alone. 3) Inhibition of antral and duodenal motility by ethanol was not abolished by anyy one of the receptor blocking agents such as adrenergic alpha and beta, buscarinic, or histaminergic H-1 and H-2 receptor blocking agents. By the above resutls, it may be concluded that ethanol inhibits the motility of the duodenum, but excites or inhibits the motility of the gastric antrum. It is likely that the inhibitory effect of ethanol is it derect action on the smooth muscle, and the excitatory effect is mediated by a mechanism related with histamine and acetylcholine.
Acetylcholine ; Alcoholic Beverages ; Atropine ; Beverages ; Chlorpheniramine ; Cimetidine ; Depression ; Duodenum* ; Embolism, Air ; Ethanol* ; Gastrointestinal Diseases ; Gastrointestinal Motility ; Gastrointestinal Tract ; Hexamethonium ; Histamine ; Muscle, Smooth ; Pharmacology ; Phentolamine ; Poaceae ; Pyloric Antrum ; Rabbits ; Relaxation ; Stomach