rs-100329 and cyclazosin

The spleen is a reservoir for circulating blood cells, and can contract to expel them.. We have investigated the adrenoceptors involved in isometric contractions of rat spleen produced by noradrenaline (NA) and the α. Contractions to NA were antagonized by both the α. Contractions of rat spleen to adrenergic agonists involve α

Topics: Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Animals; Dose-Response Relationship, Drug; Male; Muscle Contraction; Norepinephrine; Phenylephrine; Piperazines; Prazosin; Quinazolines; Quinoxalines; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Spleen; Thymine; Yohimbine

We have investigated the ability of alpha(1)-adrenoceptor antagonists to affect the hyperthermia produced by methylenedioxy methamphetamine (MDMA) in conscious mice.. Mice were implanted with temperature probes under ether anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg(-1)) was administered subcutaneously 30 min after vehicle or test antagonist or combination of antagonists and effects on body temperature monitored.. Following vehicle, MDMA produced a hyperthermia, reaching a maximum increase of 1.8 degrees C at 140 min. Prazosin (0.1 mg kg(-1)) revealed an early significant hypothermia to MDMA of -1.94 degrees C. The alpha(1A)-adrenoceptor antagonist RS 100329 (0.1 mg kg(-1)), or the alpha(1D)-adrenoceptor antagonist BMY 7378 (0.5 mg kg(-1)) given alone, did not reveal a hypothermia to MDMA, but the combination of the two antagonists revealed a significant hypothermia to MDMA. The putative alpha(1B)-adrenoceptor antagonist cyclazosin (1 mg kg(-1)) also revealed a significant hypothermia to MDMA, but actions of cyclazosin at the other alpha(1)-adrenoceptor subtypes cannot be excluded.. More than one subtype of alpha(1)-adrenoceptor is involved in a component of the hyperthermic response to MDMA in mouse, probably both alpha(1A)- and alpha(1D)-adrenoceptors, and removal of this alpha(1)-adrenoceptor-mediated component reveals an initial hypothermia.

Topics: Adrenergic alpha-Antagonists; Adrenergic Uptake Inhibitors; Animals; Body Temperature; Fever; Male; Mice; N-Methyl-3,4-methylenedioxyamphetamine; Piperazines; Prazosin; Quinazolines; Quinoxalines; Receptors, Adrenergic, alpha-1; Thymine

The contribution of different subtypes of alpha1-adrenoceptors in the lumbosacral spinal cord to the control of the urinary bladder was examined in urethane-anesthetized rats. Bladder pressure was recorded via a transurethral catheter under isovolumetric conditions. Drugs were administered intrathecally at the L6-S1 segmental level of spinal cord. RS-100329 (an alpha1A-antagonist) in doses of 25, 50, and 100 nmol significantly decreased bladder-contraction amplitude by 38%, 52%, and 95%, respectively, whereas (+)-cyclazosin (an alpha1B-antagonist) significantly decreased bladder-contraction amplitude (48% reduction) only in a 50-nmol but not a 100-nmol dose. Fifty nanomoles of RS-100329 and (+)-cyclazosin increased bladder-contraction frequency by 54% and 44%, respectively. BMY7378 (an alpha1D-antagonist), in doses of 25, 50, and 100 nmol, did not change bladder activity. These studies suggest that reflex-bladder activity is modulated by two types of spinal alpha1-adrenergic mechanisms: 1) alpha1A- or alpha1B-inhibitory control of the frequency of voiding reflexes presumably mediated by an alteration in the processing of bladder afferent input and 2) alpha(1A)-facilitatory modulation of the descending efferent limb of the micturition-reflex pathway. Spinal alpha1D-adrenoceptors do not appear to have a significant role at either site.

Topics: Anesthesia, General; Animals; Brain Stem; Efferent Pathways; Female; Injections, Spinal; Locus Coeruleus; Models, Neurological; Muscle Contraction; Piperazines; Pressure; Quinazolines; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Reflex; Thymine; Urethane; Urinary Bladder