Reference

Desensitization of the b-adrenoceptor of lymphocytes from normal subjects and patients with phaeochromocytoma: studies in vivo

Desensitization of the b-adrenoceptor of lymphocytes from normal subjects and patients with phaeochromocytoma: studies in vivo. Greenacre, J. K.; Conolly, M. E. (Dep. Clin. Pharmacol., R. Postgrad Med. Sch., London, Engl.). Br. J. Clin. Pharmacol., 5(3), 191-7 (English) 1978. CODEN: BCPHBM. ISSN: 0306-5251. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Section cross-reference(s): 14, 15 Treatment of normal subjects with oral salbutamol [18559-94-9] (12-16 mg/kg/day for 10 days), or with inhaled salbutamol (3000 mg/day for 8-10 days) decreased lymphocyte b-adrenoceptor responsiveness as measured by cyclic AMP [60-92-4] elevation by isoprenaline [7683-59-2]. A 48 h infusion of isoxsuprine [395-28-8] (10 mg/h) markedly depressed lymphocyte b-adrenoceptor responsiveness. Prolonged elevation of endogenous catecholamines caused by pheochromocytoma was also assocd. with a marked depression of lymphocyte b-adrenoceptor responsiveness. Diminished b-adrenoceptor response apparently occurs as a response to prolonged exposure to b-adrenoceptor agonists. The diminished response previously obsd. in asthmatic subjects can be explained on a similar basis and does not indicate an inherent cellular defect. The possible clin. significance of such changes in asthmatics are discussed.

Development of a pulmonary technique to assess inhaled bronchoactive agents in the conscious rhesus monkey

Development of a pulmonary technique to assess inhaled bronchoactive agents in the conscious rhesus monkey. Weissberg, Robert M.; Bradshaw, John B.; Garay, Gabriel L. (Dep. Exp. Pharmacol., Syntex Res., Palo Alto, Calif., USA). J. Pharmacol. Exp. Ther., 205(1), 246-54 (English) 1978. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 2 (Hormone Pharmacology) Section cross-reference(s): 1 A technique using conscious rhesus monkeys was developed and utilized to evaluate airway reactivity to histamine phosphate (I phosphate) [51-74-1] and subsequently det. how the airway response to I was modified by aerosolized isoproterenol sulfate [299-95-6], salbutamol [18559-94-9], and prostaglandin E1 [745-65-3] pretreatment. The exptl. animals were initially sedated with ketamine in order to implant a pleural catheter or to introduce an esophageal balloon intranasally. The monkeys, seated in a specially constructed primate chair, were then placed in a plethysmograph. Tidal vol., pleural pressure, airflow, and heart rate were recorded, and the appropriate pulmonary signals were processed by an on-line computer to obtain a breath-to-breath readout of dynamic compliance and resistance. Aerosolized antagonists, given in increasing doses, were evaluated for their ability to block I-induced decreases in tidal vol. and dynamic compliance and increases in airway resistance and breathing rate. Isoproterenol was ~5 times more effective than salbutamol in blocking I-induced pulmonary changes. At the highest tested concn. (1%) isoproterenol but not salbutamol increased tidal vol., breathing frequency, and heart rate. Prostaglandin E1 (0.1%) aerosol produced aberrant respiratory patterns and coughing in some animals. This irritant effect of prostaglandin E1 on ventilation made it difficult to evaluate its activity in decreasing I-induced airway changes. The conscious monkey appears to be a suitable model to evaluate both bronchodilator and irritational properties of bronchoactive agents under physiol. conditions.