Volume 126, number 2 FEBS LETTERS April 1981 DECREASED SENSITIVITY TO a2 ADRENERGIC AMINES, ADENOSINE AND PROSTAGLANDINS IN WHITE FAT CELLS FROM HAMSTERS TREATED WITH PERTUSSIS VACCINE J. Adolf0 GARCiA-SAINZ Depa~tmnen zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA to de Bioenerg&icu, Centro de Investigaciones en Fisiologia Cetrrlar, Universidad jVacional Attttinorm de Jlkxico, Apartado Postal 70400, MPxico 20, DF, Al&co Received 4 March 1981 1. introduction The release of insulin from pancreatic islets is inhibited by a-adrenergic activation and is increased by stimulation of /3-adrenoceptors [ 11. ol-Adreno- ceptors have been divided into 2 subtypes, (Y~ and 012, by their affinities for agonists and antagonists [2] and their underlying me~hanisln of signal transduction [3]. The a-adrenoceptor involved in the regulation of plasma insulin level is of the az subtype [4]. cr,-Adreno- ceptors are linked in an inhibitory fashion to adenyl- ate cyclase [3,5,6]. The decrease in blood insulin level due to cu-adreno- ceptor activation is effectively blocked by pertussis vaccination in rats 171. This effect of the vaccine seems to be due to a protein produced by zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA BorcIetella pertussis [8,9]. Hamster adipocytes have az-adrenergic receptors linked in an inhibitory fashion to adenylate cyclase [3,5]. Activation of these receptors decreases basal and stimulated cyclic AMP levels and lipolysis [3 ,S, lo]. The possibility that administration of per- tussis vaccine to hamsters may alter the sensitivity of their adipocytes to a,-adrenergic amines was studied. The results show that administration of pertussis vaccine to hamsters markedly decreases the sensitivity of their adipocytes to a,catecholamines. Further- more, it was found that such decrease in sensitivity is not exclusive to c+adrenergic amines but it is common to other agents such as adenosine and prosta~andil~s. 2. Materials and methods Epinephrine, isoproterenol, theophylline and pros- taglandin E, (PGE&) were obtained from Sigma Chem- 306 ical Co. ~-(L-2-p~~enyl-isopropyl)-adellosi~le (PIA), adenosine deaminase, glycerokinase, glycerophosphate dehydrogenase and NAD’ were obtained from Boehringer-Mannheim. Collagenase from Chstridiunz histolyticum (lot 4OC190) and bovine serum albumin (fraction V) (lot U13707) were obtained from Worthington and Armour Pharmaceutical Co., respec- tively. Clonidine was a generous pift of Boehringer- Ingelheim. Pertussis vaccine (strain 509, lot 29-090) was obtained from the National Institute of Hygiene (Secretaria de Salubridad y Asistencia, MCxico). Golden hamsters were fed ad libitum. Pertussis vaccine was injected intraperitonea~y (-IO” organ- isms). Animals were used 3-9 day after a single injec- tion. White adipocytes were isolated and incubated as in [5,10]. Cyclic AMP accumulation and glycerol release were determined as in [5 ,I 0 J. 3. Results The level of cyclic AMP in the absence of hormones was slightly higher in adipocytes from pertussis-treated hamsters than in control adipocytes (42 + 10 com- pared to 29 rt 2 pmol/l O6 cells, respectively; means + SEM of 6 determinations in duplicate in each case). Isoproterenol, a pure P-adrenergic agonist, produced a dose-dependent increase in the level of cyclic AMP (fig.1). The maximal accumulation of the cyclic nucleotide was not affected in adipocytes from per- tussis-treated hamsters. However, a decreased accu- mulation of cyclic AMP in response to the lowest dose of isoproterenol used (10” M) was observed in fat cells from pertus&sensitized hamsters (fig. 1). Epinephrine, an a+adrenergic agonist, produced a