The adrenoceptors involved in the increase in diastolic pressure and heart rate elicited by i.v. administration of pilocarpine to the pithed rat were assessed using as pharmacological tools the alpha 1-adrenoceptor antagonist prazosin, the alpha 2-adrenoceptor antagonist rauwolscine, the beta 1-adrenoceptor blocker atenolol and the beta 2-adrenoceptor blocker ICI 118,551. Pilocarpine indirectly activated vascular alpha 1- and cardiac beta 1-adrenoceptors. By using the M-1 antagonist pirenzepine and the mixed M-1/M-2 antagonist dexetimide, pilocarpine was shown to be a mixed M-1/M-2 agonist. Pilocarpine initiated antagonistic effects on intrasynaptic alpha 2-adrenoceptor-mediated pressor responses and not on those triggered by extrasynaptic alpha 2-adrenoceptors. During vasopressin infusion to counteract a possible vasodilator action of pilocarpine, it was demonstrated that pilocarpine indirectly activated alpha 1- and alpha 2-adrenoceptors. The results support the hypothesis that intra- and extrasynaptic alpha 2-adrenoceptors comprise different populations and that the neuronal control of alpha 2-adrenoceptors is mediated by ganglionic M-2 receptors.
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Compr Psychoneuroendocrinol
November 2024
Swedish University of Agriculture, Department of Applied Animal Science and Welfare, Skara, Sweden.
This article summarizes my scientific work and describes some personal experiences during this period. After my basal medical training (MD) (1971), I obtained a PhD in pharmacology (1976) and ended up as a professor of Physiology. My initial studies were within the field of gastroenterology.
View Article and Find Full Text PDFBrain Res Bull
October 2024
Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address:
Here we assess whether neuropathic pain hypersensitivity is attenuated by spinal administration of the imidazoline I-receptor agonist LNP599 and whether the attenuation involves co-activation of α-adrenoceptors. Spared nerve injury (SNI) model of neuropathy was used to induce mechanical hypersensitivity in male and female rats with a chronic catheter for intrathecal drug administrations. Mechanical sensitivity and heat nociception were assessed behaviorally in the injured limb.
View Article and Find Full Text PDFEur J Pharmacol
October 2024
Division of Pharmacology, School of Pharmacy, Cardiff University, Cardiff, United Kingdom.
Neuropsychopharmacology
December 2024
University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue, K1Z 7K4, Ottawa, Canada.
Addition of dopamine (DA)/serotonin (5-HT) partial agonists to 5-HT/norepinephrine (NE) reuptake inhibitors are commonly used to enhance the antidepressant response. The simultaneous inhibition of 5-HT and NE transporters with venlafaxine and its combination of brexpiprazole, which blocks the α-adrenergic autoreceptor on NE terminals, could constitute a superior strategy. Anesthetized rats received venlafaxine and brexpiprazole for 2 and 14 days, then the firing activity of dorsal raphe nucleus 5-HT, locus coeruleus NE, and ventral tegmental area DA neurons were assessed.
View Article and Find Full Text PDFMol Cell Neurosci
September 2024
Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey.
Microglia are immune cells that play important roles in the formation of the innate immune response within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiple protein complex that is crucial for innate immunity, and excessive activation of the inflammasome for various reasons contributes to the pathogenesis of neurodegenerative diseases (NDs). β-adrenoceptor agonists have become the focus of attention in studies on NDs due to the high synthesis of β-adrenoceptors in the central nervous system (CNS).
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